I /^ DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl EY 00003-15 IMDD 'ERIOD COVERED October 1, 1986 to Sqprterrber 30, 1987 riTLE OF PROJECT (60 chartcfen or less Title must tit on one line between the toniers ) RTcirnacology of Oculau: CJcrplicatians 'RINCIPAL INVESTIGATOR (Ust ottier professional personnel below ttte Principal Investigator ) (Name, title, laboratory, and institute aflihation) PI: Peter F. Kador Ri.D. Research Chemist IMOD, NEI Others: Yoshio Akagi Sanai Sato Tsuyoshi Tarmnoto Gurley, Rebecxa Katrina Anristrong M.D. Fh.D. Visiting Scientist M.D. Visiting Associate Ri.D. Visiting Scientist M.S. Biologist B.A. Guest Worker OOPERATING UNITS (H any) None >B/BRANCI- laboratory of Mechanisms of Oculeir Disease SECTION Sectican of Molecular Fharmaoology NSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 OTAL MAN-YEARS 5.5 PROFESSIONAL: 4.0 OTHER 1.5 :hECK APPROPRIATE BOX(ES) Zl (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither tUMUARY OF WORK (Use standard unreduced type Do not exceed ttw space provided ) Ihe events leading to the onset of various ocular complications are being studied inaddition to nethods for their potential phannacolo^ical contr ol. Z^^^Y^^Il ^ relationships between the enzymes aldose reductase and aldehyde ^iP.^v^V°?r^^ °^ retincpathy, catar act, p^il functio n andflS^ changes, and keratopathy induced by diabetes or galactose mia are being investigated. Methods for either delaying or preventing the onset of these Sl^'°^ ^^""""^ ^ phamacological control of these enzymes are also beir^ ^.>^^?^^'^^'T^^°" °^ ^^^ ^^'P^ °f cataracts are also be/jig studied ^^well^ methods for cxjntrolling their onset through p^^arrracological H^ nffi Tifii DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00011-13 CB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 characters or less Title must fit on one Ime betweer) the borders.) Pigment Dispersion With and Without Glaucoma PRINCIPAL INVESTIGATOR (Ust other prolessiortal personnel below the Principal Investigator ) (Name, title, laboratory, and institute afliliation) PI; Others: Muriel I. Kaiser-Kupfer M.D. Head, Section on Ophthalmic CB, NEI Genetics and Pediatric Ophthalmology Carl Kupfer Lessie McCain Sandeep Jain M.D. R.N. M.D. Director Clinical Technician Visiting Fellow NEI CB, NEI CB, NEI COOPERATING UNITS (il any) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS 1.35 PROFESSIONAL: 1.25 OTHER: .1 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided ) The purpose of this project is to compare patients with and without glaucoma having pigment dispersion syndrome. The data acquired may enable a determina- tion of the risk of patients with pigment dispersion syndrome to developing glaucoma as well as add to understanding of the pathology of the disease. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00015-22 LRCMB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 characters or less Title must fit on one line between the borders.) The Cell Biology of the Vertebrate Retina PRINCIPAL INVESTIGATOR (Ust other professional personnel below the Principal Investigator ) (Name, title, latxiralory. and institute affiliation) PI; Paul J. O'Brien Others: Robert St. Jules Ph.D. Ph.D. Head, Section on Cell Biology Staff Fellow LRCMB, NEI LRCMB, NEI COOPERATING UNITS (if any) Department of Anatomy, University of Toronto (M. J. Irons) LAB/BRANCH Laboratory of Retinal Cell and Molecular Biology SECTION Section on Cell Biology INSTITUTE AND LOCATION NEI. NIH. Bethesda. Maryland 20892 TOTAL MAN-YEARS 1.6 PROFESSIONAL 1.6 OTHER 0.0 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues E (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided ) The post-translational modifications of rhodopsin include acylatlon, glycosylation and chromophore addition. All appear to take place in the rod inner segment. The resulting molecules exhibit a slightly higher molecular weight than the mature rhodopsin in the outer segment and thus can be distinguished. The role of the palmitate residues is unknown but could be related to membrane assembly. The addition of the vitamin A chromophore seems to be essential for intracellular transport of the opsin protein to the Golgi and to the outer segments. The addition of galactose residues may be a requirement for normal outer segment disc formation as it appears to be present only in the rhodopsin molecules found in the plasma membrane and basal folds. The polyphosphoinositide pathway has been detected in rat rod outer segments thus extending the known distribution of this pathway from invertebrates and cold- blooded vertebrates to warm-blooded vertebrates. The role of this pathway in either transduction or light adaptation may be universal. A manganese-dependent 5 '-nucleotidase that cleaves cytidine monophosphate has been found to become highly active In rod outer segment tips at the time of disc shedding. It has been isolated, partially purified and characterized and could provide insight into new mechanisms related to the shedding process. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER J01 EY 00016-20 LRCMB I PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE Of PROJECT (BO cfmracnrz or mss 77n* must tn or on* Imt Omtwttn trm 6oaMfl.> The Biochemistry of Normal and Dystrophic Retinas PRINCIPAL INVESTIGATOR fL/lI offwf prolastion»l personnel Otiow m» PnncipH Ini/tstigttof ) (Namt. tm». laDorttory, mm} msmam tftumtion) Pi! Paul J. O'Brien Ph.D. Head, Section on Cell Biology LRCMB, NEI COOPERATING UNITS (K any) School Of Veterinary Medicine, University of Pennsylvania (G. Aguirre) LAB/BRANCH Laboratory of Retinal Cell and Molecular Biology SECTION Section on Cell Biology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 0.2 PROFESSIONAL; 0.2 OTHER: n.n CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews D (b) Human tissues 13 (c) Neither SUMMARY OF WORK (Ust ttvxive unrwaucuO lypt Do not »tc—elow the Phncipal Investigator ) (Name, title, laboratory, and institute affiliation) PI: David Lee Robinson Ph.D. Others: John W. McClurkin Ph.D. Caroline Kertzman Ph.D. Irene Letvin M.D. Edmond FitzGibbon M.D. Lance M. Optican Ph.D. Barry J. Richmond M. D. Timothy Gawne Ph.D. Research Physiologist LSR NEI Guest Worker LSR NEI IRTA LSR NEI Clinical Fellow NINCDS Clinical Fellow LSR NEI Research Engineer LSR NEI Senior Surgeon, PHS LNP NIMH Physiologist LNP NIMH COOPERATING UNITS (if any) LAB/BRANCH Laboratory of Sensorimotor Research SECTION Visuomotor Integration Section INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20205 TOTAL MAN- YEARS: 2.2 PROFESSIONAL: 1.0 OTHER: 1.2 CHECK APPROPRIATE BOX(ES) K (a) Human subjects D (a1) Minors n (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided ) We studied the responses of neurons to stimulus movement: that generated by real motion in the environment, by saccadic eye movements, and by smooth pursuit eye movements. Cells in the pulvinar discharge to real movement during periods of fixation but not when a saccadic eye movement causes the visual stimulation. However, these same cells do respond to the visual stimulation induced with pur- suit eye movements. Many of these cells have a pause in their activity when an animal makes eye movements in total darkness, and it may be this inhibitory pro- cess which prevents them from responding with eye movements in the light. Neu- rons in the lateral geniculate nucleus respond in all three conditions: during fixation and with both types of eye movements. Cells in the superior colliculus are similar to those in the pulvinar, they respond to real motion during fixation and with pursuit movements but not with saccadic eye movements. These data show that some parts of the brain are influenced by the behavioral context in which visual stimulation occurs whereas others are not. We tested other pulvinar cells for their excitability after saccadic eye movements. Many respond better to light just after an eye movement than during fixation. Such changes may be related to the analysis of new data with each change in eye position. Other pul- vinar cells are very selective for the frequency of stroboscopic stimulation; they respond very strongly to pulses at 4 to 6 per second. Frequently, they respond better to later stimuli in a train than to the first stimulus. Cells in the lateral geniculate nucleus have a wide variety of temporal response patterns which encode the details of visual stimulus patterns. Normal humans respond fas- ter to a visual target when its spatial location is correctly indicated by a cuing light than when the location is incorrectly cued. The hypothesis is that the cue draws attention to its location and thereby facilitates reaction times. Patients with progressive supranuclear palsy who cannot make vertical eye move- ments are nonetheless able to move their attention in that direction. '^*«,^ r,c.. ■J^-*J mK-f^*^ . DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl EY 00049-09 LSR PERIOD COVERED October 1, 1986, to September 30, 1987 TITLE OF PROJECT (80 characters or less We must tit on one ftne between tt>e borxlers.) Cerebral Cortical Mechanisms for Eye Itovements and Visual Attention PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator j (Name, title, laboratory, and institute affiliation) PI: Michael E. Goldberg M.D. Chief, NMS LSR, NEI Others: Mark A. Segraves Ph.D. Rolf Boch Ph.D. Edmond J. FitzGibbon M.D. Gregory B. Stanton Ph.D Senior Staff Fellow LSR, NEI Visiting Fellow LSR, NEI Senior Staff Fellow LSR, NEI Guest Researcher LSR, NEI COOPERATING UNITS (if any) LAB/BRANCH Laboratory of Sensorimotor Research SECTION Neuro-Ophthalmologic Mechanisms Section INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: 5.0 PROFESSIONAL; 3.0 OTHER: 2.0 CHECK APPROPRIATE BOX(ES) H (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided.) The activity of single neurons in the prefrontal cortex that projects to the frontal eye fields has been studied in a number of visual and oculomotor tasks. Neurons in this region are visually responsive and show two sorts of activity before the beginning of a saccade: presaccadic enhancement and presaccadic reac- tivation. These results suggest that the prefrontal cortex participates in the planning of visually guided saccades. Monkeys trained on a short saccadic adaptation paradigm learn quickly to change the amplitude of their saccades. Stimulation of the superior colliculus in the short term adapted case yields the same saccades as the unadapted case. The activity of some single neurons in the superior colliculus shows evidence of this adaptation: When a monkey makes a saccade of adjusted amplitude in response to a visual stimulus, some collicular neurons discharge before saccades ordinarily not associated with activity from those neurons. These observations were extended to a longer-term adaptation paradigm. One or more extraocular muscles were weakened by injection of botulinum toxin, and the non-paretic eye masked. The monkeys adapted the gain of their eye movements so that the seeing, weak eye made close to normal saccades and the non-seeing, normal eye made saccades of much larger amplitude than normal. Stimulation of the superior colliculus resulted in the production here too of saccades that did not reflect the adaptation process. A class of patients with formal reading scores within the normal range who nonetheless consider themselves to be poor readers were found to have a higher than normal amount of unwanted rapid eye movements (square wave jerks) during visual fixation, and a higher than normal amount of backward eye movements during reading. Fixational instability did not correlate with performance on a quanti- tative assessment of skeletal motor functions which correlates with attentional deficit disorder in children. I DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00060-09 CB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (BO characters or less Title must tit on one lirte between the borOers ) Visual Function and Ocular Pigmentation In Albinism PRINCIPAL INVESTIGATOR (Usi other prolessK>nal penonrtel below me Principal Investigator ) (Name, title, laboratory, ana institute affiliation) PI: Muriel I. Kalser-Kupfer M.D. Head, Section on Ophthalmic Genetics and Pediatric Ophthalmology CB, NEI Others: Lessie McCain Rafael Caruso Doris J. Collie R.N. Clinical Technician M.D. Visiting Scientist A. A. Health Technician CB, NEI CB, NEI CB, NEI COOPERATING UNITS (li any) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS .65 PROFESSIONAL; .35 OTHER ^3. CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use stanaara unreOuceti type Do not exceed the space provioea.) Patients with hypomelanotic disorders such as ocular albinism, oculocutaneous albinism, Chediak-Higashl disease, Hermansky-Pudlak syndrome, and iris transillumination defects are being recruited to determine visual function in these conditions and to evaluate its course over time. Family members are evaluated to attempt to determine factors which may identify the hetrozygous state. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00062-11 CB PERIOD COVERED October 1 , 1986 to September 30, 1987 TITLE OF PROJECT (80 chartclen or less Title must In or one line between me botOers.) Irido-Corneal-Endothellal (ICE) Syndrome PRINCIPAL INVESTIGATOR (Ust other prolessionml personrtel Delow ttte Principal Investigator ) (Name, title, laboratory. anC institute attiUation) PI: Others: Muriel I. Kaiser-Kupfer M.D. Carl Kupfer Lessie McCain Manuel Datiles M.D R.N. M.D. Head, Section on Ophthalmic Genetics and Pediatric Ophthalmology Director Clinical Technician Visiting Scientist CB, NEI NEI CB, NEI CB. NEI COOPERATING UNITS (il any) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: .35 PROFESSIONAL; .25 OTHER: .1 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews D (b) Hunnan tissues D (c) Neither SUMMARY OF WORK (Use stanaera unreHuced type. Do not exceed ttte space proviOeO.) This project was formerly titled "Progressive Essential Iris Atrophy." Patients are being recruited with progressive essential iris atrophy with or without associated corneal disease. Information is being gathered to evaluate the clinical features and course of the disease process and to investigate aqueous humor dynamics in both affected and unaffected eyes. ■^p" «■■*-»■* DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl EY 00065-10 OSD PERIOD COVERED October 1, 1986, to September 30, 1987 TITLE OF PROJECT (80 cfttracMrz or l»ss TiOt must ht on orn lint between the bomert.) Physiological studies of the Primate Visual System PRINCIPAL INVESTIGATOR (List ottier proteujonti personnel below the Pnncipel lnv9St)gator) (Name, title, leboretory. erxJ mstnute ethuatiofi) PI: Others: Francisco M. de Monasterio, M.D., D.Sc. Medical Officer OSD, NEI Edna P. McCrane B.S. Biologist OSD, NEI COOPERATING UNITS (» any) Lions of District 22C Eye Bank and Research Foundation, Inc (Seabrook, Maryland), LAB/BRANCH Office of the Scientific Director SECTION INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 1.00 PROFESSIONAL; 0.50 OTHER; 0.50 CHECK APPROPRIATE BOXo »I«-«H DEPARTMENT OP HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT ZOl EY 00069-10 LI PERIOD COVERED October 1, 1986 to September 30. 1987 TITLE OP PROJECT (BO cfttfcnrt c mu Tnm must trt on ont unt omrw»n me txtrvmn.) Immune Responses to Ocular Antigens PRINCIPAL INVESTIGATOR ILat otrmr pratunnai p»rtonn»i oiow tn» fmcipai tnnsiigamr ) (Sam*, ont. luxxutofy, »na mtmut* tffmaoon) PI: Igal Gery Ph.D. Others: Shigeto Hirose M.D. Hiroki Sanui M.D. Takao Tanaka M.D. LiHong Hu M.D. -Roberto de Bara M.D. Head, Section on Experimental Immunology Visiting Fellow Visiting Fellow Visiting Fellow Visiting Fellow Senior Staff Fellow LI, NEI LI, NEI LI, NEI LI, NEI LI, NEI LI, NEI COOPERATING UNITS (H any) LAB/BRANCH Laboratory of Immunology SECTION _ Section on Experimental Immunology INSTITLITE AND LOCATION NIH, NEI, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 7.95 PROFESSIONAL; 7. 84 OTHER. 0.11 CHECK APPROPRIATE BOXfES) D (a) Human subjects D (a1) Minors □ (a2) Interviews C3 (b) Human tissues D (c) Neither SUMMARY OF WORK (U»t mnoam unmaucaa rype Do not ameff me tpae* pronome.) This project is aimed at learning about the pathogenesis of inflammatory eye diseases which are designated "uveitis". In experiments with human material we have found that by using a sensitive assay, lymphocytes from a portion of healthy donors react in culture to retinal-specific antigens, S-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP) . Furthermore, clones of lymphocytes with specificity toward S-Ag were cultivated from the blood of a healthy donor. It is proposed that such lymphocytes, when activated, could play a pivotal role in the pathogeneis of uveitic conditions. The major seg- ment of this project has focused on the animal disease, experimental autoimmune uveitis (EAU) , which is considered a model for certain human conditions. Main findings: (1) Bovine IRBP is highly uveitogenic in primates, while monkey IRBP did not induce EAU at similar doses. Antibodies from monkeys immunized with bovine IRBP cross reacted well with monkey IRBP but the cross reaction was poorly detected by cellular reactions. (2) Fragments of IRBP of known amino acid sequence were found highly uveitogenic in rats, thus making it possible to identify the uveitogenic site(s) of this molecule. (3) A cell line of rat lymphocytes specific for IRBP was established in culture. The line cells produced EAU at numbers as low as 500,000/rat and will be useful for future studies on the pathogenesis of this disease. (4) Rats of the W/F inbred strain are poor responders to S-Ag induced EAU. This low susceptibility was found to be due to a poorly developed cellular immune response to S-Ag. (5) EAU develop ment was found to be markedly enhanced by local damage to rat eyes. The data suggest that local injury could facilitate immune -mediated inflammation in the human eye as well. (6) Animals immunized with IRBP or S-Ag develop pineal- itis, in addition to uveitis. The type of inflammation is different, however, in the two organs of affected rats and we report here that the "acute" inflam- mation in the eye disappears within 10 days while the "chronic" infiltration in the pineal lasts for at least 3 months. PHC «n.n ,c.., ..^. c»o •<«••<• DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBE3 ZOl EY 00070-10 LRCMB PERIOD COVERED October 1. 1986 to September 30. 1987 TITLE OF PROJECT (80 ctttrtcmn of /•« TiV» must tit on ont lint between th« borxltrt.) Vitamin A and Ocular Tissues PRINCIPAL INVESTIGATOR (List ott>»r protessiontl personnti below W« Pnncipal Invtstigitor ) (Namt. Of%, ttboratory. tntJ insvtutt iftilittion) PI: Barbara Wiggert Ph.D. Head, Section on LRCMB, NEI Biochemistry Others: Ling Lee M.S. Chemist Michael Redmond Ph.D. Staff Fellow Umi Hirose M.D. Guest Worker Gerald J. Chader Ph.D. Chief LRCMB, NEI LRCMB, NEI LRCMB, NEI LRCMB, NEI COOPERATING UNITS (» any) LSU Eye Center, New Orleans, LA (N. Bazan, T. Reddy) LAB/BRANCH Laboratory of Retinal Cell and Molecular Biology SECTION Section on Biochemistry INSTITUTE AND LOCATION NEI. NIH. Bethesda. Maryland 20892 TOTAL MAN-YEARS; 2.8 PROFESSIONAL: .^ OTHER; 1-n CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews [1 (b) Human tissues D (c) Neither SUMMARY OF WORK (Us» starxSut unnducad typa Do not »*c»u» Pnnap*! Imusiigaior ) (Maim. vo». mDormmry. ana nttnun attmaoon) PI: Robert B. Nussenblatt M.D. Clinical Director NEI Others: Alan G. Palestine M.D. Head, Section on Clinical Immunology LI, NEI Chan M.D, Senior Staff Fellow LI, NEI Leake M.S. Biologist LI, NEI Hirose M.D. Visiting Fellow LI, NEI COOPERATING UNITS (II any) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTrrLTTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 0.91 PROFESSIONAL: 0.21 OTHER. 0.7 CHECK APPROPRIATE BOX/ES) Q (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither Summary op work (Un itanoarv unnauoaa typa. Do not a toa ae me toaoa pr o maae.) In vitro cellular immune functions and lymphocyte subsets are being studied in a masked method in patients with ocular toxoplasmosis, pars planitis, Behcet's disease, geographic choroiditis, and chorioretinitis of unknown origin. Crude ocular antigens, purified uveitogenic soluble antigen (S-antigen) , IRBP of the retina, and uveitogenic fractions of the retinal S-antigen are being used in a lymphocyte microculture technique to evaluate the presence of cellular immune memory to ocular tissues. In addition, purified antigens from the toxoplasmosis organism are also being tested in this in vitro system. A subgroup of patients with posterior uveitis has been identified as having this immunologic memory. Lymphocyte subsets in the blood and in the eye are being defined in these patients by monoclonal antibodies. These results shed light on the basic mechanisms of uveitis and may be used as a guide for specific immunologic therapy. The serum from these patients is also being evaluated. PROJECT NUMBER DEPARTMENT OF HEALTH AND HUMAN SERVICES ■ PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT Z01 EY 00078-10 LOP ' PERIOD COVERED October 1, 1986, to September 30, 1987 TITLE Of PROJECT (BO characnn or l*u Tiut must ht on on» knt Ocrwaan (rw ttorxMn.) Histopathology of Human Dystrophies and Degeneration PRINCIPAL INVESTIGATOR (Lssx amtr profestional personnel o*/o>v m» Principal Inmtigator ) (Ntmt. OVe. »Dorttoiy. tnO mstnutt iftuiuoon) PI: Merlyn M. Rodrigues M.D.,Ph.D. Head, Section on LOP, NEI Ophthalmic Pathology Others: Joseph Hackett B.S. Biologist LOP, NEI COOPERATING UNITS (» any) Department of Ophthalmology, University of Iowa, Iowa City LAB/BRANCH Laboratory of Ophthalmic Pathology SECTION Section on Ophthalmic Pathology INSTITUTE AND LOCATION National Eye Institute, NIH, Bethesda, MP 20205 TOTAL MAN- YEARS: 0.2 PROFESSIONAL: 0.1 OTHER. 0.1 CHECK APPROPRIATE BOXer prolessKyiBl personnel below Itm Prmcipel Investigalor ) (Name, title, laboratory, ana mstnute aflilietion) PI: Muriel I. Kaiser-Kupf er M.D. Head, Section on Ophthalmic CB, NEI Genetics and Pediatric Ophthalmology Others: Lessie McCain Rafael Caruso Kent Hlgglns R.N. Clinical Technician M.D. Visiting Scientist Ph.D. Expert CB, NEI CB, NEI CB, NEI COOPERATING UNITS (it any) The Howard Hughes Medical Institute Laboratory and the Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland (Davi'd L. Valle. M.D.) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI. NIH. Bethesda. Maryland 20892 TOTAL MAN- YEARS _Li PROFESSIONAL; OTHER CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF V^ORK (Use stanaart) unreOuced type Do not exceed me space proviOeci.) Patients with gyrate atrophy of the choroid and retina are examined systematical- ly to confirm the diagnosis. Skin fibroblats of affected patients and family members are grown In tissue culture and assayed for ornithine aminotransferase activity. The results will be evaluated for correlation with the presence of homo- or heterozygosity for the disease trait. Patients will be given a trial of pyrldoxine to see if serum concentration of ornithine can be reduced, and, if so, the patient will be classified as a "responder," and treatment with pyrldo- xine will be continued. Nonresponder and responder patients will be placed on a low arglnine, low protein, diet with supplemental amino acids and observed for an arrest or Improvement of their disease. If patients are not considered eligible for the diet or If they appear unable to comply with the dietary regimen they will be followed to record the natural progress of the condition. Patients with other forms of retinal degeneration, such as retinitis pigmentosa, fundus flavimacula- tus. Juvenile retlnoschisis, are also examined and their courses are compared with gyrate atrophy patients. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00084-09 CB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (BO characters or less Title must tit on one line between the boroers ) Anterior Chamber Anomalies Associated with Glaucoma or Ocular Hypertension PRINCIPAL INVESTIGATOR (Usi other prolessional personnel below the Principal Investigator ) (Name, title, laboratory, and mstilute atliliation) PI: Carl Kupfer M.D, Director NEI Others: Muriel I. Kaiser-Kupfer M.D. Lessie McCain Manuel B. Datiles Paul Edwards R.N. M.D. M.D. Head, Section on Ophthalmic Genetics and Pediatric Ophthalmology Clinical Technician Visiting Scientist Visiting Fellow CB, NEI CB, NEI CB, NEI CB, NEI COOPERATING UNITS (i1 any) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS 0.60 PROFESSIONAL; 0.40 OTHER .2 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMAR't' 0^ WOhk lUse stanaa'o unreoucec type Do no: etceec the space p':..iaez ] With recent embryological research indicating the role of the neural crest in contributing to all connective tissues anterior to the lens epithelium, the group of developmental anomalies of the anterior chamber with glaucoma or ocular hypertension is being reviewed. DEPARTME^^r OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT ZOl EY 00092-09 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE Of PROJECT (BO efrmcmrt or mu Tiv must tn on on* km o»rw»»n me Doroan.) HLA, ABO, and B-cell Alloantigens and Ocular Inflammatory Disease PRINCIPAL INVESTIGATOR (Lai om»' prvumnai pertormmi b»Km tr>» Pnnap*: Investigator ) (Nemt. on* moorttory. »na nsmw anmanai) PI: Robert B. Nussenblatt M.D. Clinical Director NEI COOPERATING UNITS (f any) Center for Drugs and Biologies, Food and Drug Administration (Kamal Mittal, M.D.) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 0.03 PROFESSIONAL; 0.03 OTHEa CHECK APPROPRIATE BOXfES) El (a) Human subjects D (a1) Minors D {a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Us* tanow unrtaocaa type. Do not cxcvac me to»o* prwioae.) Patients with ocular toxoplasmosis, pars planitis, Behcet's disease, chorioretinitis of unknown origin, are being studied to determine the phenotype frequency of the HLA, ABO, and B-cell alloantigens. Because the B-cell alloantigens or DR antigens are thought to play a role in the immunologic response to antigens, these findings will complement other immune uveitis studies being simultaneously carried out. m e*o 1 1 «**i« IBfliBI DEPARTMENT OF HEALTH AND HUMAN SERVrCES - RUBUC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBES ZOl EY 0009A-09 LI PERIOD COVERED October 1. 1986 to September 30, 1987 TITLE Of PROJECT (SO cttartcmrz or ku fitm must tn on oo* on* o»rw»n m* tforomn.) Immune Mechanisms In Experimental Autoimmune Uveitis PRINCIPAL INVESTIGATOR (Lat omur protmtnonu partonnti D»o» ir» fmapti Inrtttigator ) (Stmt. m» Mooratory. •no msmun tHmaOon) Clinical Director PI: Robert B. Nussenblatt M.D. Others: Alan G. Palestine M.D. William Leake M.S. Rashid Mahdi Head, Section on Clinical Immunology Biologist Biologist NEI LI, NEI LI, NEI LI, NEI COOPERATING UNITS (* mny) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTn-UTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 0.69 PROFESSIONAL; 0.2A OTHER. 0.45 CHECK APPROPRIATE BOX(ES) D (a) Human subjects O (a1) Minors D (a2) Interviews D (b) Human tissues lEI (c) Neither SUMMARY OF WORK (Un sanow unr*aucoe rype. Do not axcvaO rrw xpaca pronnota.) Lewis rats and non-human primates, immunized at a site distant to the eye with the retinal soluble antigen (S-antigen) in complete Freund's adjuvant, develop experimental autoimmune uveitis (EAU) . Lymph node cells and peripheral lymphocytes from immunized animals manifested significant cellular immune responses measured by the lymphocyte culturing technique. The cyclosporines, a family with specific anti-T-activity, have been found to be exceptionally effective in protecting rats with EAU. Attempts at local immunosuppressive therapy in order to prevent EAU have begun. Topical and periocular CsA have been used in order to evaluate its effectiveness in EAU. Newer cyclosporines, particularly D&G, have been evaluated in this model, with their efficacy compared to that of cyclosporine A. Ciamexone, a drug with immunopotentiating characteristics, has always been utilized in this model. An in vitro model of specific S-antigen antibody production is being developed. PMS 60*0 (Pwv 1/B4I CO tl<-*»tow tr>» Pnncipal tnvtitigttor j (Namt. me. lalx>ralory. ana msmuta tftiliation) PI: Merlyn M. Rodrigues M.D., Ph.D. Others: Joseph Hackett B.S. Reginald Gaskins Head, Section on LOP, NEI Ophthalmic Pathology Biologist LOP, NEI Histologist LOP, NEI COOPERATING UNITS (K any) LAB/BRANCH Laboratory of Ophthalmic Pathology SECTION Section on Ophthalmic Pathology INSTITUTE AND LOCATION National Eye Institute, NEI, Bethesda, MD 20205 TOTAL MAN- YEARS: PROFESSIONAL: OTHER; 0.3 0.2 0.1 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (b) Human tissues [E (c) Neither D (a1) Minors D (32) Interviews SUMMARY OF WORK (Ust sianoarc unraaucaa typa Do not •xcveO m« spaca provioaa.) Patients with localized ocular diseases or with ocular manifestations of systemic disease are examined clinically, and photographic documentation is made of significant findings. Biopsy specimens or autopsy eyes from these patients are examined by electron microscopy and histochemical stains. Studies are performed on patients with ocular manifestations of systemic diseases. Forty patients with acquired immunodeficiency syndrome (AIDS) were examined for ocular abnormalities. Twenty of these patients died and the eyes were obtained for culture and histologic examination. These patients have multiple opportunistic infections and neoplasms as the result of a severe depression of cellular immunity. Fifty percent of all patients with AIDS and 75$ of the autopsy group have ocular signs attributable to AIDS. Ocular findings were confined to four major categories: cytomegalovirus (CMV) retinitis (10 patients), retinal cotton wool spots (11 patients), conjunctival Kaposi's sarcoma (2 patients), and neuro-ophthalmic motility abnormalities (3 patients). Cytomegalovirus retinitis was a significant cause of visual loss. Seven of ^40 autopsy eyes had hand-motion or worse vision prior to the patient's death because of CMV and progressed to involve the entire retina in three to six months resulting in a gliotic retina membrane. Disseminated systemic histoplasmosis was observed in a patient with AIDS. In 3 patients, the effect I of argon laser treatment was shown to be ineffective in halting the spread of I cytomegalovirus in patients with AIDS. Immunohistocheraical stains are performed on patients with retinitis pigmentosa and retinoblastoma to test for the presence of neuronal and glial proteins. Electron microscopy is also performed in selected cases. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30, 198? PROJECT NUMBER Z01 EY 00105-08 LMOD TITLE OF PROJECT (80 chartctan or lais T1O9 must ht on ont lint Oarwten ttta bonlars.) Structure and Composition of Lens Crystallins with Respect to Cataractogenesis PRINCIPAL INVESTIGATOR (Ust of/)»r prt>lassion»l ptrsonnal balow ttia Pnncipal Invastigaior ) (Nama. Vtla. latxyalory, and instnuta aftiliaoon) PI: J. Samuel Zigler, Jr. Ph.D. Research Biologist LMOD, NEI Others: Valerie A. Lucas Qing-ling Huang Xinyu Du Ph.D. Visiting Fellow M.D. Visiting Fellow M.D. Visiting Fellow LMOD, NEI LMOD, NEI LMOD, NEI COOPERATING UNITS (0 any) Jules Stein Eye Institute, UCLA Medical School (J. Horwitz); Department of Chemistrj^, Adelphi University (F. Bettelheim); Department of Ophthalmology, University of Tennessee (H. M. Jernigan, Jr.) LAB/BRANCH Laboratory of Mechanisms of Ocular Diseases SECTION Section on Cataract INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 2.6 PROFESSIONAL: 2.6 OTHER: 0.0 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews E] (b) Human tissues D (c) Neither SUMMARY OF WORK (Uia standarO unraducad typa Do not ancaad ttia tpaca providad ) The crystallins are the basic structural elements of the ocular lens. These globular, structural proteins are evolutionarily conservative proteins with structures uniquely suited to their functional role, ie, to form highly organized and densely packed protein matrices which are optically transparent. Our studies are oriented toward elucidation of the mechanisms of cataract development and the role of changes either in the structure or the composition of the crystallins in opacification of the lens. With respect to structural modifications to crystallins, we are particularly interested in the modifications induced by oxidative stress since the lens is exposed in vivo to an unusual level of such stress. We have previously investi- gated the potential effects of the high concentration of H2O2 in the aqueous humor on intact lenses in organ culture, finding that H2O2 is toxic whereas stronger but short-lived oxidants (free radicals) derived from it show little toxicity when produced in the fluids surrounding the lens. In model systems we have now shown that when generated intracellularly the reverse is true. H2O2 itself causes little damage, but upon conversion to hydroxyl radicals or related species the crystallins are rapidly oxidized. Thus not only the oxidizing species, but the location in which it is generated is critical in determining its potential for producing lens damage. We have recently found that zeta-crystallin, a lens protein unique to guinea pigs [Which we discovered and partially characterized. Is absent or present in sharply reduced amounts in the lenses of guinea pigs with hereditary congenital nuclear cataracts. This finding gives us an ideal opportunity to investigate in an animal model system the effect of a major change in crystallin composition. iMi 1 DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl EY 00109-07 LSR PERIOD COVERED October 1, 1986, to September 30. 1987 TITLE OF PROJECT (80 characters or less Title must fit art one line between ttte borders.) Visual Motion Processing in the Primate Brain PRINCIPAL INVESTIGATOR (List Other professional personnel below the Principal Investigator ) (Name, title, laboratory, end institute aftiliation) PI: Robert H. Wurtz Ph.D. Others: Hidehiko Komatsu Ph.D. Dwayne S. G. Yamasaki Ph.D. Jean-Pierre Roy M.D. Ph.D. Chief LSR, NEI Visiting Scientist LSR, NEI Guest Researcher LSR, NEI Guest Researcher LSR, NEI COOPERATING UNITS (if any) LAB/BRANCH Laboratory of Sensorimotor Research SECTION Visuomotor Integration Section INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: ^.0 PROFESSIONAL: 2.0 OTHER: 2JL n (b) Human tissues K (c) Neither CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided.) We have continued our study of visual motion processing in the cerebral cortex. Our investigations concentrated on two areas of cortex that are largely devoted to motion processing, the middle temporal area (MT) and the medial superior tem- poral area (MST). In area MST we investigated the response of cells to motion of the visual background as the monkey made a pursuit eye movement. We could iden- tify two types of cells. One type responded vigorously to large field stimula- tion and this response frequently was synergistic with the pursuit response. Another group of cells respond to small moving spots and are largely insensitive to motion of the background. In area MT, we have investigated changes in the receptive field size of cells adjacent to a region damaged by a neurotoxin that impairs the monkey's ability to generate a pursuit eye movement. We found that the receptive fields did not expand selectively to cover the area of the visual field previously covered by the cells damaged by the neurotoxin. Many cells did, however, show an expansion of their field size in all directions. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl EY 00114-07 LOP PERIOD COVERED October 1, 1986, to September 30, 1987 TITLE OF PROJECT (80 characters or less Title must lit on one line befween the borders.) Histopathologic Studies of Animal Models of Human Ocular Disease PR_INCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator j (Name, title, laboratory, and Institute affiliation) Head, Section on LOP, NIH Ophthalmic Pathology Biologist LOP, NIH Research Chemist LVR, NIH Chief, Laboratory of Vision Research PI: Merlyn M, Rodrigues M.D., Ph.D. Others: Joseph Hackett B.S. Barbara Wiggert Ph.D. Geraldn Chader Ph.D. COOPERATING UNITS (if any) LAB/BRANCH Laboratory of Ophthalmic Pathology SECTION Section on Ophthalmic Pathology INSTITUTE AND LOCATION National Eye Institute, NIH, Bethesda, MD 20892 TOTAL MAN-YEARS: 0.2 PROFESSIONAL: 0.1 OTHER: 0.1 CHECK APPROPRIATE BOX(ES) B (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided.) Immur.ocytocheraical staining of fresh frozen rhesus monkey retinas was performed using indirect immunofluorescence and immunoperoxidase (avidin-biotin- complex). Affinity-purified antibodies to interphotoreceptor retinoid-binding protein (IRBP) obtained from rabbits was used to localize IRBP on frozen sections. Fresh frozen pineal glands from the same species were stained by the avidin-biotin-peroxidase method. In addition, retinas from rod-dominant and cone-dominant species were examined. Immunocytochemical staining revealed localization of IRBP in the interphotoreceptor space of peripheral equatorial and posterior retina, with marked decrease in staining in the fovea. A transition zone was noted at the ora serrata, where staining was present in the peripheral retina up to the ora serrata, but was absent in ciliary epithelium. Cone-dominant retinas (chick and turtle) showed lack of reactivity to IRBP. Rod-dominant rat retina showed localization of IRBP to the interphotoreceptor space. Primate and rat pineal showed immunocytochemical localization of IRBP. Spontaneously occurring anterior chamber segment anomalies in DBA/2 mice were studied by slit-lamp biomicroscopy and light and transmission electron microscopy (TEM). The opacities consisted of aggregates of basophilic material in the superficial stroma which stained positively for elastin TEM revealed that they were electron dense and extracellular. Iris abnormalities consisted of stromal atrophy and proliferation of corneal endothelium and basement membrane across the iris surface and trabecular meshwork. The corneal opacities seen in DBA/2 mice show a striking similarity to those which characterize familial band- shaped nodular keratopathy, a form of corneal elastosis. c i c DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT ZOl EY 00115-07 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT fBO cfmcnrt or »si Tiu» must tr on on* im* o»iw»»n vm oorvn.l Cyclosporine Therapy in Uveitis PRINCIPAL INVESTIGATOR (Lttl ormr proitujona! perjonnti osfow tn» Pnnc**/ invmttigMiof ) (Nmrrm. Btw. MoofBrory, •no ntman tlfmaoofij PI: Robert B. Nussenblatt M.D. Clinical Director NEI Others: Alan G. Palestine M.D. Edward J. Holland M.D. Roberto de Bara M.D. Francois Roberge M.D. Richard P. Wetzig M.D. Head, Section on Clinical LI, NEI Immunology Senior Staff Fellow LI, NEI Senior Staff Fellow LI, NEI Visiting Associate LI, NEI Senior Staff Fellow LI, NEI COOPERATING UNITS (f any) LAB'B RANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 1.A9 PROFESSIONAL; 1.48 OTHER; 0.01 CHECK APPROPRIATE BOX(ES) [El (a) Human subjects D (a1) Minors D (a2) Interviews □ (b) Human tissues D (c) Neither SUMMARY Of WORK CUM na/toaro unnajotC rypt Do not azcMO tttt Mpaet Cyclosporine, an endecapeptide fungal product with specific anti-T-cell characteristics, will be administered to patients with sight-threatening ocular inflammatory disease of non-infectious origin who have failed on either corticosteroid or cytotoxic agent therapy. This will be done to test cyclosporine 's efficacy in the treatment of uveitis. Within the context of these ongoing studies, the effect of hydergine on reversing cyclosporine induced nephrotoxicity is being evaluated in a randomized, masked, cross-over study. Additionally, selected patients whose uveitis is well controlled on cyclosporine for one year or more are undergoing kidney biopsies to evaluate the long term effects of this agent. AM^iMU&a 6»0 tl«**<> DEPARTME^^■ OF HEALTH AND HUMAN SERVICES • PUBUC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PEBIOD COVERED Octobe r 1, 1986 to September 30, 1987 TITLE Of PROJECT (80 cnamamn or m*s Tiv must hi on on» unt MrwMn trm Ooivmn.) Oculomotor Disorders in Human Subjects projEC' mumbe= ZOl EY 00117-07 CB PRINCIPAL INVESTIGATOR (iat orr»' proltuiona: ptrtonrm: o»tow m* fmapti Innttigttor ) (Ntmt m*. mooratory. ana mimun tltmaoonj PI: James Carl M.D. Senior Staff Fellow CB, NEI Others: Edmond FitzGibbon M.D. Reuben Gellman Ph.D. Senior Staff Fellow Staff Fellow LSR, NEI CB, NEI COOPERATING UNPrS (» mnyj LAB/BRANCH Clinical Branch SECTION Neuro-ophthalmology Section INSTrrLTTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 1.7 PROFESSIONAL: 1.7 OTHER: CHECK APPROPRIATE BOXfES) E] (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY Of WORK (Un tmnavc unmaucmc rypt Do not •z»eO tne soac* promote.) The continuing emphasis of this project has been to collaborate with the Laboratory of Sensorimotor Research in studying oculomotor disorders in human subjects. The computerized methods for recording and analysing eye movements pioneered by the LSR have been applied to a variety of clinical eye movement disorders . An ongoing series of experiments established a set of normative values for human performance of several of the oculomotor subsystems, particularly the saccadic and pursuit systems. The major advances in these areas were extensions of neurophysiological work done in the LSR on non-human primates. The major findings included a description of the motion processing needed to keep the eyes following a moving target by saccades and pursuit movements. The human brain requires about 75 milliseconds to begin to follow moving stimuli, but an accurate assessment of the stimulus velocity develops over an additional 100 milliseconds. Studies on the role of the basal ganglia in eye movement processing continued with a study of patients with progressive supranuclear palsy, with particular attention to the abnormalities of vertical eye movements in spite of relatively preserved horizontal eye movements. These patients were also examined for attentional deficits. Additional ongoing projects included following patients with a variety of neurological disorders of metabolism such as Gaucher's, Fabry's and Niemann-Pick disease. PmS 6040 mev i/M) c*o t<<-«<* DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986, to September 30, 1987 PROJECT NUMBER ZOl EY 00122-07 OSD TITLE OF PROJECT (80 characMrs (y teM Trtte must tit on one lint between ttie borders ; Anatomical Studies of the Primate Visual System PRINCIPAL INVESTIGATOR (Ust other prottssiooaJ personnel below the Pnncipal Investigator ) (Name. otle. laboratory, and institute affiliation) PI: Others: Francisco M. de Monasterio, M.D., D.Sc. Medical Officer OSD, NEI Edna P. McCrane Marvin B. Shapiro Catherine J. Szellga 6.S. M.S. Biologist Research Mathematician Normal Volunteer OSD, NEI LSM, DCRT CC COOPERATING UNITS (If any) Howe Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, (Boston, Massachusetts), and Laboratory for Statistical Methodology, DCRT. LAB/BRANCH Office of the Scientific Director SECTION INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS; 1.20 PROFESSIONAL: 0.50 OTHER: 0.70 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews E] (b) Human tissues D (c) Neither SUMMARY OF WORK (Use stanOarxi unreduced type Do not exceed the space provided.) This project involves the study of the anatomical properties and organization of cells in the visual system of primates, with emphasis on the retina and the visual cortex. The blue-sensitive cones of the macaque retina were selectively labelled using tissue-reactive dyes injected into the vitreous humour, and the spatial properties of the retinal point pattern of these cones was examined. We have developed a model describing the degree of regularity and structure of the cone pattern. To evaluate the topographical relationship between the cones and ganglion cells of the area centralis of human and macaque retina, especially in the fovea, we have also studied and quantified the radial displacement between photoreceptors and postreceptoral cells, and measured the density of both cones and ganglion cells. Correction for such displacement permits the topographical comparison of the densities of these two cell types in terms of visual angle; this comparison allows for an estimate of the overall degree of convergence of cones to ganglion cells, and provides boundaries for the areal coverage factor of these cells. We have also compared the density of ganglion cells to that of cells of the lateral geniculate nucleus (LGN), both for the parvocellular and the magnocellular streams; this comparison provides information about central magnification properties in this nucleus. PHS 6040 (Rev 1/84) CPO ti4-e<( m i C c c DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00123-07-CB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 cnaraciers or less Trile must tit on one line between Itte bomers ) Clinical Psychophysics of the Visual System PRINCIPAL INVESTIGATOR (Usi other prolessionBi personnel Oe/ow me Principal Investigator ) (Name, title. latx>ralory. ana institute atliliationj PI: Muriel I. Kaiser-Kupfer M.D. Others: Rafael C. Caruso Kent E. Higgins Ralph D. Gunkel M.D. Ph.D. O.D. Head, Section on CB, NEI Ophthalmic Genetics and Pediatric Ophthalmology Visiting Scientist CB, NEI Expert CB, NEI Ophthalmic Physicist CB, NEI COOPERATING UNITS (it any) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS .65 PROFESSIONAL .35 OTHER .3 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use stentiaro unreajceO type. Do not exceea trie space proviaed.) The visual function of patients with ocular diseases or lesions in the visual pathways and of normal subjects is measured with psychophysical techniques. These data are correlated with those obtained with electrophysiological tests of visual function. The results obtained contribute to the diagnosis of ocular and neural disorders that affect vision, and are needed to characterize their nature and evolution. They are also valuable in the assessment of the effect of different forms of treatment on the outcome of these diseases. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 0012^-07 LRCMB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (BO c/i«/«cf»fS Of fss Vtlt must tit on one Una tjetwBtn m« borOen.) Metabolism of the Retina and Pigment Epithelium PRINCIPAL INVESTIGATOR (Liit othti protessiontl perjonnai fieto* tf>* Pnnapal lnvtst)gttor ) (Namt. rni*. taboratory. and msmuta aftilmtion) PT. r.or'sTr^ .1 Phartor- Ph H Th i of LRTMR. NRT PI: Gerald J. Chader Others: Marlissa Campbell Robert Waldbillig R. Theodore Fletcher Ph.D Chief Ph.D. Staff Fellow Ph.D. Expert M.S. Chemist LRCMB, NEI LRCMB, NEI LRCMB, NEI LRCMB, NEI COOPERATING UNITS (» any) LAB/BRANCH Laboratory of Retinal Cell and Molecular Biology SECTION Section on Gene Regulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 2.2 PROFESSIONAL; 2.2 OTHER: 0.0 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) interviews El (b) Human tissues D (c) Neither SUMMARY OP WORK (Usa standard unnducad type Do not atcaad tha apaca profridad.) Internal and external messengers have been studied which code for aspects of growth, development and function of normal retinal cells and also which affect differentiation of retinoblastoma cells in culture. Insulin receptors are present in high concentration in normal retinal cells and in retinoblastoma cells indicating a role for insulin in retinal function. Also, extracellular matrix components such as laminin have been found to affect differentiation of cultured human retinoblastoma cells. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00126-06 LMDB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (BO characters or less Title must lit on one line between the borders) Crystallin Genes: Structure, Organization, Expression, and Evolution PRINCIPAL INVESTIGATOR (List other prolessional personnel below the Principal Investigator) (Name, title, latMratory, and instrtute affiliation) PI: Joram Piatigorsky Ph.D. Chief LMDB, NEI Ana B. Chepelinsky Graeme J. Wistow Cynthia Jaworski Diana Parker liana Keshet Bernd Sommer Ph.D. Expert LMDB, NEI Ph.D. Visiting Associate LMDB, NEI M.S. Chemist LMDB, NEI B.A. Chemist LMDB, NEI Ph.D. Fogarty Fellow LMDB, NEI Ph.D. Guest Worker LMDB, NEI COOPERATING UNITS (if any) See next page. LAB/BRANCH Laboratory of Molecular and Developmental Biology SECTION INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 12,6 PROFESSIONAL 12.6 OTHER: 0.0 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided.) We have continued to characterize crystallin gene structure although greater emphasis was placed on expression. Sequences have been completed, or nearly completed, for the human and chicken oA- and the chicken BBl -crystallin genes. Intron 1 of the human aA-crystallin gene has been shown to encode an insert exon found so far only in rodents. The 5' flanking sequence of the murine aA-crystallin gene has been dissected into a distal, enhancer-like element and a proximal element. Both elements bind specifically to different nuclear proteins of embryonic lens cells, as judged by gel retardation experiments. Transfection studies using the pSVOCAT expression plasmid have shown that the 5' flanking sequence of the chicken 61 -crystallin gene contains an upstream region (-603 to -120) that appears to down-regulate promoter activity. Strong promoter activity has been identified in the 5' flanking sequence of the chicken 6B1 -crystallin gene, initiating our efforts to study the regulation of this class of crystallins. The human and murine aB-crystallin genes have been isolated; the promoter has been identified in the murine gene. A transgenic mouse facility has been established, and several progeny carrying hybrid genes using crystallin promoters have been born. Numerous crystallins have been shown to be enzymes: e-crystallin is lactate dehydrogenase, 6-crystallin is argininosuccinate lyase and T-crystallin is enolase, indicating the pragmatism of lens evolution, i.e., the use of enzymatic proteins in a new structural role. Finally three crystallin polypeptides have been identified in the jellyfish lens; one (35K) has been purified and partially sequenced. PHS 6040 (Rev 1/84) 6PO 9l4>Blt t C c c DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00127-11 LMDB PERIOD COVERED October 1, 1986 to September 30, 198? TITLE OF PROJECT (80 characters or less Title must fit on one Ime between the borders ) Plasma Membrane Composition and Biosynthesis in Chick Lens Fibers and Epithelia PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator ) (Name, title, laboratory, and institute afliliationj PI: Peggy Zelenka Ph.D. Geneticist LMDB, NEI Luke Pallansch John Talian Ph.D. Staff Fellow Ph.D. IRTA Fellow LMDB, NEI LMDB, NEI COOPERATING UNITS (it any) Flora de Pablo Paul Russell David Beebe M.D. Diabetes Branch/NIDDK Ph.D. LMOD, NEI Ph.D. USUHS, Bethesda, MD LAB/BRANCH Laboratory of Molecular and Development Biology SECTION Section on Cellular Differentiation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS; 2.0 PROFESSIONAL: 1.3 OTHER; 0.7 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues El (c) Neither SUMMARY OF V(/ORK (Use standard unreduced type Do not exceed the space provided.) This project seeks to determine whether lens fiber differentiation is associated with alterations in plasma membrane lipids or proteins. Previous results have indicated that phosphatidlyinositol degradation ceases when lens epithelial cells differentiate to form lens fiber cells. Since phosphatidylinositol is rich in arachidonic acid, a precursor of prostaglandins and leukotrienes, the metabolites of arachidonic acid produced by lens cells are being characterized. Comparison of metabolites synthesized before and after the onset of fiber cell formation demonstrates that the loss of a lipoxygenase pathway metabolite is associated with differentiation and the concommitant increase in c-myc mRNA. Plasma membrane proteins being investigated include the insulin and IGF receptors, and the membrane associated protein calpactin I. Specific insulin and IGF receptors have been demonstrated on both lens epithelial cells and lens fiber cells throughout embryonic development; a marked decrease in insulin receptors is associated with fiber cell formation. Calpactin I has been shown to be a major component of the EDTA extractable protein (EEP) of lens membranes. This protein binds both phospholipids and actin, and may thus be involved in anchoring the cytoskeleton of the lens to the membrane. c t c DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00132-06 LMDB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (SO characters or less Title must tit on one line between the bottlers ) Molecular Biology of Photopigments PRINCIPAL INVESTIGATOR (Ust other prolessional personnel ttelow the Principal Investigator ) (Name, title, latxjratory. and institute attiliation) PI: Toshimichi Shinohara Ph.D. Head LMDB, NEI Others: Masahiko Tsude M.D., Ph.D. Benjamin Amaladoss Ph.D. Kunihiko Yamaki M.D., Ph.D. Viji Singh Ph.D. Visiting Fellow Visiting Assoc. Visiting Fellow Visiting Assoc. LMDB, NEI LMDB, NEI LDN, NICHD LMDB, NEI COOPERATING UNITS (H any) Larry Donoso M.D., Ph.D. Wills Eye Hospital Philadelphia, PA LAB/BRANCH Laboratory of Molecular and Developmental Biology SECTION Section on Molecular Biology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: PROFESSIONAL OTHER; 0.0 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews B (b) Human tissues B (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided ) We have investigated the structure, function, evolution and immunogenic sites of the retinal S-antigen (^8 K protein) and its gene. The complete amino acid sequences of human, bovine and murine retinal S-antigen have been determined by partial protein sequencing and cDNA sequencing. Coding sequences of S-antigen cDNAs from human, bovine and murine retinas have approximately 80% similarity. In contrast, noncoding sequences of these cDNAs have at most only 30J similarity. The polypeptide sequences of S-antigen from human, bovine and murine retinas are also very similar (-83$). Immunogenic sites of bovine S-antigen were determined, as were two monoclonal antibody binding sites (epitopes) and two uveitopathogenic sites (named M and K) using 20 different chemically synthesized oligopeptides. The minimum size required for EAU induction was also determined. M peptide was 12 and K peptide was 20 amino acids long. These small peptides contain all the necessary information for the induction of EAU. EAU was also observed following the adaptive transfer of T cell lymphocytes from Lewis rats which were previously immunized with M peptide, indicating that experimental autoimmune uveitis (EAU) induced by M was also a T cell mediated autoimmune response. The clinical and histopathologic features of EAU induced with M peptide were similar to those developed with native S-antigen. The M12 peptide of S-antigen from humans and mice has an identical sequence to that of bovine S-antigen. Searching the NBRF data bank revealed no extensive sequence homology between S-antigen and other proteins, although some sequence similarity was apparent with a-transducin. Interestingly, these include the sites subject to ADP-rlbosylation by petussis toxin and the phosphoryl binding sites. PHS 6040 (Rev 1/84) 6PO •<4.»1l V c c c DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30. 1987 PROJECT NUMBER Z01 EY 00135-15 TITLE OF PROJECT (80 chtrmcfri or Itss Trth must tit on on* lint Ottwten ttm borOft.) Biochemistry of Retina and Pigmented Epithelium in Health and Disease PRINCIPAL INVESTIGATOR (Ust oth»r proftiiiontJ personnel below th* Pnnapal Investigator j (Nimt. otle. laborttoiy, and mstrtuTa affiliation) PI: Helen H. Hess M.D. Medical Officer (Research) DSD. NEI COOPERATING UNrrS (» any) Veterinary Resources Branch, DRS, NIH LAB/BRANCH Off ire of the Scientific Director. NEI SECTION INSTITUTE AND LOCATION Natinnsi Fyp Tn<;titiite. NIH. Bethesda. Maryland 20892 TOTAL MAN-YEARS: 1,3- PROFES5IONAL: in OTHER; JL3. CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Usa standard unreOuced typa Do not atctud tha tpaca provtOtd.) The effects of nutrition, oxidation, and other environmental factors (light intensity or darkness) on the incidence and progress of posterior subcapsular opacities (PSO) associated with retinal degeneration are being studied in Royal College of Surgeons (RCS) rats, in which rod photoreceptor outer segment debris accumulates secondary to a phagocytic defect in the retinal pigmented epithelium. Evidence has been obtained that oxidative changes In polyunsaturated fatty acids in the debris lead to water-soluble toxic aldehydes that can be detected in the vitreous, and are toxic to lens membranes. Several diets prevent the mature cataracts, and dark-rearing prevents the PSO detectable microscopically. Pink-eyed dystrophic rats exposed to constant light of 25 footcandles beginning (1) at 20-23 postnatal days or (2) at birth, had histopathological changes similar to those in some naturally occurring human posterior subcapsular cataracts (PSC), such as in retinitis pigmentosa. Many mature cataracts also occur with cyclic light of low intensity at a time when a large amount of rhodopsin debris is present. In the RCS dystrophic rat, freed retinal may have a prolonged lifetime (owing to slowed conversion of retinal to retinol and to poor regeneration of rhodopsin). Freed retinal may act as a photosensitizer to generate singlet oxygen, a highly energetic oxidant for polyunsaturated lipids. Prevention of the cataracts by dark rearing or by feeding a purified diet with llpid-soluble antioxidants (vitamin E, BHT * Beta-carotene) supports the hypothesis of lipoperoxi dative damage to the lens. Principles established with this readily manipulated animal model may have significance for slowing or preventing human iPSC and mature cataracts. c c c DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 001ier professional personnel Oelow ffte Principal Investigator ) (Name, title. latx>ratory ana mstnute atlilialion) PI: Muriel I. Kaiser-Kupfer M.D. Others: Lessie McCain R.N. Head, Section on Ophthalmic CB, NEI Genetics and Pediatric Ophthalmology Clinical Technician CB, NEI COOPERATING UNITS (rl any) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS .15 PROFESSIONAL .1 OTHER CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use stanoara unreouceO type Do not exceed tne space provioeti j The Interinstitute Medical Genetics Program and the Genetics Clinic, supported by the Clinical Center, offer a multidisciplinary approach to patients with genetic disease (Z01 CP 05139-0^4 CEB). Involved in the program are researchers from all Institutes. Patients evaluated in the clinic reporsent a broad spectrum of genetic disease. During the last year, approximately ^25 individuals were seen, representing approximately 100 different disease categories. Due to the high frequency of ocular involvement in many of the cases, almost all the patient were evaluated by Clinical Branch staff of were discussed in consultation. The Clinic serves as a source of interesting case material concerning patients with Inherited or developmental abnormalities of the visual system. In addition to the Genetics Clinic, patients are seen for genetic consultation at the Maryland School for the Blind. This experience has resulted the recruit- ment of patients into Clinical Branch protocols. DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT ^u^'BES ZOl EY 00172-05 CB 'ERiOD COVERED October 1, 1986 to September 30. 1987 ■|TL£ OF PROJECT (BO cfttrtzttr) c Zeis Titit must lit on one line tmrwten m» borOtri ) Senile Macular Degeneration >BINCIPAL INVESTIGATOR (Jjsl other proftsnonti personnel belo* the Pnncipel Investigator ) (Heme, title, leboretoiy, »nij msttute etfiliation) PI: Muriel I. Kaiser-Kupfer M.D. Head, Section on CB, NET Others: Carl Kupfer Monique S. Roy M.D. M.D. Head, Section on Ophthalmic Genetics Director Visiting Scientist NEI CB, NEI OOPERATING UNITS (* any) None AaBRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology NSTITUTE AND LOCATION NEI. NIH. Bethesda. Maryland 20892 rOTAL MAN-YEARS. Ji2 PROFESSIONAL: Jil. OTHER. :mECK APPROPRIATE BOX(ES) S] (a) Human subjects Q (al) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use stanaera unreOuced type Do not etceea the spec* provtOaa) This Study will determine if patients with severe visual loss because of senile macular degeneration in one eye and with good vision in the second eye can be protected from severe visual loss in the good eye by the administration of vitamin E and vitamin C when exposure of the retina to light below 500 nanometers is diminished. The recruited patients will be randomly assigned either to a treated or untreated control group and examined at four-month intervals. Follow-up will continue for five years, unless an early beneficial or detrimental effect causes the study to be terminated in less than five years. PmS 6040 (R»v \lh*) DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30, 1987 PROJECT NUMBER ZOl EY 00184-05 LI TITLE OF PROJECT (80 characttrs or lets Title must ht on one line between the bonien.) Cellular Mechanisms in Uveitis PRINCIPAL INVESTIGATOR (List other protess^onal personnel below tM Pnnapal Investigator ) (Name. otle. laboratory, and institute atfiimtxinj PI: Rachel Caspi Ph.D. Visiting Associate LI, NEI Others: Robert B. Nussenblatt Francois Roberge Chi-Chao Chan William Leake Myung Kim Makoto Higuchi M.D. Clinical Director M.D. Visiting Associate M.D. Senior Staff Fellow M.S. Biologist M.D. Visiting Fellow M.D. Visiting Fellow NEI LI, NEI LI, NEI LI, NEI LI, NEI LI, NEI COOPERATING UNITS (» any) LABaRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS. PROFESSIONAL: 2.04 OTHER: 0.04 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews G (b) Human tissues U (c) Neither SUMMARY OF WORK (Use starxiare unreOucud type Do not exceed me space pronOed.) In vivo functional long-term T-cell lines and T-cell clones are developed and maintained in vitro from both peripheral blood and ocular fluids of humans and animals. The phenotype and functional properties of these cells, as well as their interaction with ocular resident cells are being studied. The goal of these studies will be to identify the immunoreactive cells and mediators involved in the intraocular inflammatory process. DEPARTMEKPr OF HEALTH AND HUMAN SERVICES ■ PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER Z01 EY 00187-OM-CB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (BO characlers or *ss Title must In on one hne between We boftiers.) The Effects of Corneal Contact Lenses on the Cornea PRINCIPAL INVESTIGATOR (Ust otrter prolessionei personnel Deiow ttte Principal Invesiigalor ) (Name, title, laboratory, and mstitule aliilianonj PI: Manuel B. Datiles M.D. Visiting Scientist Others: Carl Kupfer M.D. Lessie McCain R.N. Muriel I. Kaiser-Kupfer M.D. Director Clinical Technician Head, Section on Ophthalmic Genetics and Pediatric Ophthalmology CB, NEI NEI CB, NEI CB, NEI COOPERATING UNITS (U any) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: 0.2 PROFESSIONAL: 0.10 OTHER. 0.1 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use sianOarv unreduced type Do not exceed trie space provided.) Short- as well as long-term effects of contact lens wear on the cornea are being investigated. Changes in corneal curvature, changes in corneal epithelial morphology and changes in corneal endothelial cell morphology are being studied by specular microscopy. These data will help us understand the dynamics involved in the interaction between a contact lens and the cornea, the risk involved to corneal tissues, and how a systemic or local disorder may increase these risks. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30, 1987 PROJECT NUMBER Z01 EY 00188-OiJ CB TITLE OF PROJECT (BO characters or less Title must tn on one line berweert me borOers j Documentation and Monitoring of Opacities in the Human Lens PRINCIPAL INVESTIGATOR (Usi otner protessnynal personnel below the Principal Investigator ) (Name, title laboratory, and institute affiliation) PI: Manuel B. Datiles M.D. Others: Carl Kupfer M.D. Robert Sperduto M.D. Peter Kador Ph.D. Lessie McCain R.N. Visiting Scientist CB, NEI Director nei Head, Epidemiology Branch BEP, NEI Head, Section on LMOD, NEI Molecular Pharmacology Clinical Technician CB, NEI COOPERATING UNITS (if any) Image Processing and Analysis Laboratory, DCRT, NIH (Benes Trus, Ph.D., Chief) Clinical and Diagnostic Trials Section, NCI, NIH (Sylvan Green, M.D.) Nuclear Medicine, Clinical Center, NIH (Joseph Frank, M.D.) LAB/BRANCH Clinical Branch SECTION Section on Ophthalmic Genetics and Pediatric Ophthalmology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: 0.9 PROFESSIONAL; 0.7 OTHER 0.2 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use stanaerd unreOuced type. Do not exceed the space provided ) We are developing objective and subjective methods to monitor and document opacities in the human lens using different systems. We are presently actively recruiting patients with and without cataracts for reproducibility studies on the objective systems — the Scheimpflug cameras (Zeiss and topcon), Retroillumi- nation camera (Neitz), Specular microscope (Keeler) and laser light-scattering spectroscope (KOWA). We will also test other systems using sound (ultrasono- graphy), and nuclear magnetic resonance (magnetic resonance imaging). We are also studying subjective systems or method, such as the effects of cataracts on visual perception, contrast sensitivity, and glare, which may be useful as additional parameters in the monitoring of cataract presence, progression, or regression. PHS 6O40 (Rev MM) CO •< 4-9ie DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl EY 00189-OA LMOD PERIOD COVERED October 1. 1986 to September 30. 1987 TITLE OF PROJECT (60 chiracttrj or lass T/Oe must M on ona lint batwean ma borxJars.) Oxidation of Proteins in Cataractogenesis and Protein Kinases in Lens Function PRINCIPAL INVESTIGATOR (Ust othar proftsstonal parsonnal balow tha Pnncpal Invastigamr ) (Nama. Otia. laboratory, ana insmutt affiliation) Donita L. Garland, Ph.D. Expert * LMOD, NEI COOPERATING UNITS (» any) None LAB/BRANCH Laboratory of Mechanisms of Ocular Disease SECTION ■ Section on Cataracts INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: 1.0 PROFESSIONAL. 1.0 OTHER: 0.0 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews El (b) Human tissues D (c) Neither SUMMARY OF WORK (Usa stanOart unraOucad typa Do not axcaaa tte' pro'emonMi personnel below the Principal Investigttor ) {Heme. iwe. letxynory. and mstitult afliiiaoon) PI: Kent E. Higgins Others: Rafael C. Caruso • Monique S. Roy Francisco de Monasterio Robert Nussenblatt Ph.D. Expert M.D. Visiting Scientist M.D. Visiting Scientist M.D. Medical Officer M.D. Clinical Director CB, NEI CB, NEI CB, NEI OSD CB, NEI COOPERATING UNITS (it any) None LAB/BRANCH Clinical Branch SECTION Office of the Clinical Director INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: l.A PROFESSIONAL: 1.0 OTHER; CHECK APPROPRIATE BOX(ES) S (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither Summary of work (Use stenOtrO unreCuceC type Do not exceed tt>e space proviOeC) Spatial contrast sensitivity was used to assess losses or changes in overall visual resolution in patients having a variety of toxic, inf lainmatory, degenerative, or congenital retinal and neuro-ophthalmological disorders of the visual system. A criterion-free forced-choice physchophysical procedure was used, since this method was previously shown to minimize false positive or false negative diagnoses at initial test and to minimize spurious changes in sensitivity with repeated testing. Contrast sensitivity testing, while requiring more patient testing time, continued to be superior to conventional acuity measurements for the detection of early losses and for monitoring changes in visual resolution in patients undergoing treatment. Age-referenced normative data make it possible to distinguish contrast sensitivity loss due to ocular disorder from that expected on the basis of normal aging. A retinal image stabilization system is under construction. This system is intended to permit focal elect roretinography and high resolution microperimetry in small, localized regions of a patient's retina. Pis 6040 (R»v Mb*) DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT \UMBEB ZOl Ey 00214-.02 CB PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 cfiartct»rz or Mu TiU» must til on one line OefwMn mt borOrs ) Acquired and Congenital Color Vision Deficiencies; Mechanisms and Diagnosis PRINCIPAL INVESTIGATOR (List otttti professiona' personnai below trtt Principal Inrestigato' ) (Hame. Wf». laboratory, ana mstitjta aHiimtion) PI: Kent E. Higgins Ph.D. Expert CB, NEI Others: Francisco M. deMonasterio M.D. Rafael C. Caruso M.D. Robert B. Nussenblatt M.D. Medical Officer OSD, NEI Visiting Scientists CB, NEI Clinical Director CB, NEI COOPERATING UNITS (H any) None LA^BRANCH Clinical Branch SECTION Office of the Clinical Director INSTITUTE AND LOCATION NEI. NIH. Bethesda, Maryland 20892 TOTAL MAN-YEARS. 1.1 PROFESSIONAL: 1.0 OTHER: 0.1 CHECK APPROPRIATE BOX(ES) B (a) Human subjects D (al) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Use stanaarti unreOucad type Do not aMcee<3 O* space proynaeO ) This project involves the study of cone function in cases of color vision defects, with special emphasis on the acquired color deficiencies. Human subjects have been used for these studies which range from attempts to improve quantification of data from existing data for the purpose of designing better tests for detecting color defects secondary to ocular disorder. PmS 60*0 (Rev VM) D DEPARTMENT Of HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT P«C^ECT MUMBEr ZOl EY 00217-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OP PROJECT (BO efncnrz of mu Tnm tnun m on on* an* MiwMn m* Oo»r».; Lymphocyte Migration in Experimental Autoimmune Uveitis PRINCIPAL INVESTIGATOR (Utt otrmr prolttuont! p»rtonn»i o»ow int Pnncjp*! Intmstigtny ) (h»mt, tmt. »Doftoiy ana mtmjt* aflikaaon) PI: Others: Alan G, Palestine M.D. Head, Section on Clinical LI, NEI Immunology Robert B. Nussenblatt M.D. Consuelo Muellenberg-Coulombre Myung Kim M.D, Susan Lightman M.D. Clinical Director Chemist Visiting Fellow Visiting Fellow NEI LI, NEI LI, NEI LI, NEI COOPERATING UNITS (f mny) LASmRANCH Laboratory of Immunology SECTION Section on Clinical Immunology INSTTT JTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 0.30 PROFESSIONAL: 0.20 OTHER iLX CHECK APPROPRIATE BOXfES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues E (c) Neither SUMMARY OF WORK (Un stmnow unrwauote ryp* Do nol azcMC me MPaca pnxnoue.) Experimental autoimmune uveitis (EAU) is induced by immunization of rats and other experimental animals with S-antigen (a soluble antigen from the retina) is being investigated in this laboratory as a model of human intra-ocular inflammation. This experimental inflammation can be transferred from donor rats to naive recipients using lymphocytes harvested from the spleen or lymph nodes. Following harvesting of the cells from the donors and three days in culture with stimulating antigen, the cells are injected into the intra-peritoneal cavity and five to seven days later the recipient rats develop EAU. The disease can also be transferred using a T-helper cell line by intra-peritoneal or intra-ocular injection. The mechanism of transfer of disease is unclear. This work has used radioactively labeled lymphocytes to determine the fate of these lymphocytes after injection into the peritoneal cavity or blood during the process of the development of uveitis. The goal of this project is to understand the initiating mechanisms of inflammation in the hope that these mechanisms can be extended and applied to human inflammations. Cells from an S-Ag specific T cell line migrate into the retina and cause EAU. The kinetics of this migration are being studied. S-antigen specific cells reach the eye in greater numbers if the inflammation in the eye is induced by S-antigen than if it is induced by another mechanism. PHS 6040 (Rev 1/641 c^o ti tf*ei* DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT P«OjECT MjMBE" ZOl EY 00218-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 Ofrtcnri or mu Titm must hr on on» tnt o»rw9»n m* oorvrt.) Acquired Immune Deficiency Syndrome PRINCIPAL INVESTIGATOR ILai otrwr prottunnMi parsonntl oaow in* frtnaoai Invttigtror ) (N»m%. OD*. moorttoiy. ana nimun tflmtoofi) PI: Alan G. Palestine M.D. Head, Section on Clinical LI, NEI Immunology Others: Robert B. Nussenblatt M.D. Clinical Director NEI COOPERATING UNITS (n any) Laboratory of Tumor Cell Biology, National Cancer Institute (S. Zaki Salahuddin, Ph.D.); Laboratory of Cellular & Molecular Biology, National Cancer Institute (Dharam Ablashi, D.V.M.); Department of Critical Care Medicine, Clinical Center (Henry Nasur, M.D.); Laboratory of Tumor Cell Biology, National LABm RANCH Laboratory of Immunology SECTION Section on Clinical Immunology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 0.09 PROFESSIONAL; 0.09 OTHER; CHECK APPROPRIATE BOWES) El (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Uwi ttanaw unrwoiXXO type Do not axcveo me aoac* p^ wi ata.) Cytomegalovirus retinitis is the major cause of blindness in AIDS patients. Although we have previously shown that DHPG is effective in treating this infection, the disease relapses without continued maintenance. Maintenance therapy requires intravenous infusion and is associated with marrow toxicity. A multi-center randomized trial is currently being planned to evaluate the use of this drug. PmS wvirxt... ■"'"■ C»0 •! S'^M DEPARTMENT Of HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 cf»r»cmrz or mu TttM nual tn on on* imt tmtwtmn in* ooromn.) The Effect of Bromocriptine on Human Uveitis PROJECT MUMBE" ZOl EY 00219-02 LI PRINCIPAL INVESTIGATOR (Lat om»' prottiMionti (mrtonnt: o»K>w tn* fnnapai Imtstigimr ) (Ntmi, dm. mocnmfy. ana mmjf tthimoon) PI: Alan G. Palestine M.D. Head, Section on Clinical LI, NEI Immunology Others: Robert B. Nussenblatt M.D. Janet L. Davis M.D. David C. Herman M.D. Jeffrey C. Bloom M.D. Clinical Director Senior Staff Fellow Senior Staff Fellow Senior Staff Fellow NEI LI, NEI LI, NEI LI, NEI COOPERATING UNfTS (> any) Metabolism Branch, National Cancer Institute (Marie C. Gelato, M.D.) LAB/BRANCH Laboratory of Iraniunology SECTION Section on Clinical Immunology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 1.01 PROFESSIONAL; 1.01 OTHER; CHECK APPROPRIATE BOXfES) SI (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues D (c) Neither SUMMARY Of WORK (Utt sanoaw unrwotjctc lype. Do no! azoMO me Mpaca promotO.) In recent years there has been increasing evidence in the literature that pituitary hormones are capable of regulating the immune system. There is evidence to suggest that prolactin is an immunostimulatory hormone and that reduction of serum prolactin levels in experimental animals by hypothesectomy or bromocriptine will result in a degree of immunosuppression. This information has been applied to humans and two clinical studies have begun. Both of these are in early phase of patient recruitment. One study is a randomized trial between placebo and bromocriptine in recurrent anterior uveitis using the end point of the number of recurrences per year to determine whether or not bromocriptine is capable of regulating the immune system in these patients. The second trial focuses on the additive effects of cyclosporine plus bromocriptine in attempts to treat patients with posterior uveitis at lower doses of cyclosporine in order to reduce its concurrent renal toxicity while at the same time achieving an immunosuppressive effect. Cyclosporine and prolactin compete for binding sites on the lymphocyte. Further studies in human disease will hopefully elucidate other aspects of the neuroendocrine axis which can be utilized to regulate the immune system to treat autoimmune diseases. t^td^^OAtUbm^t—lJA^i. CO tl«*«lt DEPARTMENT Of HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBES ZOl EY 00220-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (BO cffmcnrt or mu Titf must tn on on» tnt o»iw»en trw ooexmrt.) Endocrine Modulation of Immune-Mediated Eye Disease in Rats PRINCIPAL INVESTIGATOR (Lat om»' pnHmujonn p»rtonnn 010* tn» frmcofi Invwstivatof j (Iwnt OM. maoramr,. ana nsmjH aflWaoon; PI: Alan G, Palestine M.D. Head, Section on Clinical LI, NEI Immunology Others: Consuelo Muellenberg-Coulombre Myung Kim M.D. Robert B. Nussenblatt M.D. Stephanie A. Skolik M.D. Chemist Visiting Fellow Clinical Director Research Fellow LI, NEI LI, NEI NEI LI, NEI COOPERATING UNITS (H urty] Metabolism Branch, National Cancer Institute (Marie C. Gelato, M.D.) LAfi/B RANCH Laboratory of Immunology SECTION Section on Clinical Immunology INSTrrUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 1.19 PROFESSIONAL; 0.49 OTHER. 0.7 CHECK APPROPRIATE BOX^) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues Q (c) Neither SUMMARY OF W^ORK (Urn tmnoarv unrwaucaa typt. Do not trcmtc the Mpaca prwame.) In recent years there has been increasing evidence in the literature that hormones are capable of regulating the immune system. There is evidence to suggest that prolactin is an immunostimulatory hormone and that reduction of serum prolactin levels in experimental animals by hypothesectomy or bromocriptine will result in a degree of immunosuppression. An animal model of experimental autoimmune uveitis (EAU) induced by immunization of rats with S-antigen (a soluble antigen from the retina) is used as a model for intraocular inflammatory disease. We have demonstrated that concurrent antibody production in both males and females and the incidence of uveitis in female animals but did not have a significant effect on the immune responses measured by lymphocyte proliferation. As reported before, cyclosporine in high doses (10 mg/kg) there is only partial effect. We have demonstrated that the concurrent use of bromocriptine to suppress prolactin in combination with low dose cyclosporine is more effective than either drug separately in suppressing both the incidence of disease as well as the cellular and humoral immune responses to immunization. There is evidence in the literature to suggest that cyclosporine is able to compete for binding on the lymphocyte by prolactin and that reductions in prolactin level may therefore make cyclosporine more effective. Further studies in animal disease will hopefully elucidate other aspects of the neuroendocrine axis which can be utilized to regulate the immune system to treat autoimmune diseases. The alpha adrenergic antagonist prazosin is also capable of modulating EAU in our laboratory. However, there is no decrease in cellular or humoral immune responses . DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT \UMBES ZOl EY 00221-02 LI PERIOD COVERED October 1, 1986 to September 30. 1987 TITLE OF PROJECT ISO cnmrmcnrj or mas Titm must tn on on» mrm Mrwtn m» Ooroan.) Intraocula r Class II Antigen E xpression In Endotoxin-TnHnrPH Th.P■,•^^c PRINCIPAL INVESTIGATOR (Lai om»r profstnnat (mnonrmi t»>ow r>» Pnncio*' Invtsiigno/ ) (Ntmt. mw itDormmry. ana nsmam anmaaon) PI: Alan G. Palestine M.D. Others: Myung Kim M.D. Consuelo Muellenberg-Coulombre Robert B. Nussenblatt M.D. Head, Section on Clinical Immunology Visiting Fellow Chemist Clinical Director LI, NEI LI, NEI LI, NEI NEI COOPERATING UNITS (e mny) LAB/BRANCH Laboratory of Immunology SECTION Section on Clinical Immunology INSTrrUTE AND LOCATION NEI, NIH, Bethesda. Maryland 20892 TOTAL MAN. YEARS: 0.51 PROFESSIONAL; 0.^1 OTHER: 0.1 CHECK APPROPRIATE BOXfES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues CB (c) Neither SUMMARY OF WORK (Us* ttmnotm unmajota type Do nor »xc»»e the spmot promote.) Endotoxin is a polysaccharide derived from the cell wall of gram negative bacteria. When injected into the footpad or the eye of a rat it will induce an inflammatory reaction within the eye. The mechanism of this inflammation is still unclear. However, since several types of anterior uveitis in humans appear to be linked to gram negative bacteria exposure, this is considered a relative model for anterior uveitis in humans such as Reiter's syndrome. In this study rats received E. coli endotoxin and the expression of class II antigens was studied within the eye using immunohistochemical techniques. We observed that the expression of class II antigens on the ciliary body and iris preceeded the influx of inflammatory cells into the eye and that the inflammatory cells that entered the eye were primarily neutrophils with some monocytes. No T-cells were present in the inflammatory infiltrate. The inflammatory cellular infiltrate could be inhibited by indomethacin or colchicine, however this did not alter the expression of class II antigens by the iris or ciliary body indicating that this expression is not simply a consequence of the inflammatory infiltrate but may be intimately involved with the mechanism of the expression of endotoxin induced uveitis. Corticosteroids were capable of suppressing both the cellular inflammatory infiltrate and the expression of class II antigens. The expression of class II antigens on nonlymphoid cells within the eye may be important in antigen presentation or may simply signal a phenotypic change on the cells due to the interaction of endotoxin with the cell membranes. The findings were compared with the expression of class II antigen in passive and active intraocular Arthus. DEPARTMENT OF HEALTH AND HUMAN SERVICES ■ PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT .MUMBES ZOl EY 00222-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE Of PROJECT (80 cfmcmrz or mss Titta muit tn on one Une DmTwtn tnt tnfMn.) Immunopath ology In t he Eyes with Experimental Autoimmune Uveitis (EAU) PRINCIPAL INVESTIGATOR (Lnt otrmr pmlaxsmnti penonnti Otiow the Pnnapal Invstigttof ) (Ntmt, crx. iu>or9tory. tnO msmun HhhatKyi) PI: Chi-Chao Chan M.D. Others: Robert B. Nussenblatt M.D. Igal Gery Ph.D. Rachel R. Caspi Ph.D. Barbara Detrick Ph.D. Senior Staff Fellow LI, NEI Clinical Director NEI Head, Section on Experimental LI, NEI Immunology Visiting Associate LI, NEI Expert LI, NEI COOPERATING UNITS (H tny) University of Tokyo, School of Medicine (Manabu Mochizuki, M.D.) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: 0.43 PROFESSIONAL: 0.43 OTHER; CHECK APPROPRIATE BOXe bortiers.) Immunopathology of Ocular Onchocerciasis and Otner Parasitic Diseases PRINCIPAL INVESTIGATOR (Ust other prolessionH personnel below the Pnncipaf Investigator ) (Name^ title itbp'-iiory and msmutt emimboni PI: Chi-Chao Chan M.D. Senior Staff Fellow ' LI, NEI Others: Robert B. Nussenblatt M.D. Clinical Director NEI COOPERATING UNITS (It any) National Institute of Allergy and Infectious Diseases, Clinical Parasitic Diseases Section (Eric A. Ottesen, M.D.); World Health Organization (K. Awadzi, M.D.) LAB/BRANCH Laboratory of Iinmunology SECTION Section on Immunoregulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, MD 20892 TOTAL MAN-YEARS 0.3 PROFESSIONAL; 0.3 OTHER: CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (al) Minors D (a2) Interviews IE] (b) Human tissues D (c) Neither SUMMARY Of WORK (Use standard unreduced type Do not exceed tf>e space prxxnOed.) Ocular specimens and sera from 12 patients with onchocerciasis and 10 controls were studied. A mild to moderate chronic inflammatory cellular infiltration was present in the conjunctiva of the onchocerciasis patients. T-lymphocytes were the predominant inflammatory cells with the T-suppressor subset being significantly increased in the onchocerciasis patients when compared to controls. In the onchocerciasis patients, the nonlymphoid cells in the conjunctiva and iris, such as vascular endothelia, pericytes and fibroblasts, showed an increase in expression of class II antigens. The anti-onchocerca Volvulus antibodies in the sera and aqueous humor were significantly higher in the patients compared to the controls. These findings suggest that T-cells are important in the ocular immune response to onchocerca and that expression of class II antigens on nonlymphoid cells and the humoral factors may all play a critical role in ocular onchocerciasis. Using the indirect immunoperoxidase method, autoimmune antibodies against outer segments of photoreceptors and inner neural layers of retina were identified in sera and ocular fluids from patients with onchocerciasis. These antibodies could not be absorbed by S-Ag nor IRBP. They may play a role in the retinal degeneration in onchocerciasis. PHRBtWl.a... 1/ e^o ti4.*i* DEPARTMENT Of HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBES ZOl EY 00227-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TPTLt OF PROJECT (BO cnarmcnrt or au litm must ht on on» unt otrwptn m* Oorort.) Histopathology of Pars Planitis and Experimental Autoimmune Uveitis PRINCIPAL INVESTIGATOR (Lat om»r proltsannt' prtonrmi owow tn» PnnaDti ininstigtmr / (Stmt, on* lunrmmry, tne rusoM ftmaoon) PI: Richard P. Wetzig M.D. Senior Staff Fellow LI, NEI Others: Robert B. Nussenblatt M.D. Chi-Chao Chan M.D. Barbara Detrick Ph.D. John J. Hooks Ph.D. Clinical Director NEI Senior Staff Fellow LI, NEI Expert LI, NEI Head, Section on Immunology LI, NEI and Virology COOPERATING UNITS (* any) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTTTUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 0.58 PROFESSIONAL: 0.58 OTHER CHECK APPROPRIATE BOX/ES) D (a) Human subjects D (a1) Minors D (a2) Interviews El (b) Human tissues O (c) Neither SUMMARY OF WORK (Un tmnOfC unrwauotO typt Do not •zcmO me spao* prwiaae.) Studies in animals and in patients are being carried out to determine factors influencing ocular immune responses. In an animal model, rats are immunized with S-retinal antigen to produce experimental autoimmune uveitis. Animals in one group received anti-la antibody intraperitoneally and developed the onset of uveitis significantly later and to a lesser extent than controls. Histopatho- logically, the anti-la treated animals had much less inflammation than did controls. A human eye with pars planitis was also studied immunohistologically. In the pars plana region there was an elevated helper to suppressor T-cell ratio. In addition, the snowbank area showed staining for glial fibrillary acid protein Muller cells, type IV collagen and laminin. There was staining for HLA-DR throughout the globe. The results of these studies shed light on how surface antigens effect and are transmitted by ocular immune responses. -B^r »^-" "=— •-- G^O •!««•*• DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 cnamcnn or au Tiim must tn on ont »ni oantvvn me t/orouri.) Study of Ocular Glial Cells Involvement in Uveitis PROJECT MUM6ES ZOl EY 00228-02 LI PRINCIPAL INVESTIGATOR (LSI o(rw pixMtujonti penonn»i c»tow m* Pnnupai In^^siigttor ) Ifitm*. dm. moontoiy. mna msfflut* affiMOon; PI: Francois Roberge M.D. Visiting Associate LI, NEI Others: Robert B. Nussenblatt M.D. Rachel Caspi Ph.D. Clinical Director Visiting Associate NEI LI, NEI COOPERATING UNITS (H mny) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTrrUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 0.92 PROFESSIONAL: 0.92 OTHER- CHECK APPROPRIATE BOXTES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues El (c) Neither SUMMARY OF WORK (Uu lanomw unmauc»a typt. Do not azcaec in« tpaca promome.) The work extended our ongoing study of interactions between the retinal glial Miiller cell and T lymphocytes. In an in vitro co-culture system, Miiller cells had been shown to exert a profound inhibitory influence on antigen and IL-2 driven proliferation of T helper cell lines. Investigations of the nature of the inhibitory moiety revealed that it was sensitive to proteinase. In further studies, we demonstrated that Miiller cells can produce interleukin 1 (IL-1) activity and that in conditions where their inhibitory action is removed they display the capacity to efficiently function as antigen presenting cells. PMS 60*0 (Rev 1/64) CVO (K.*!* DEPARTMENT Of HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUM6ES ZOl EY 00229-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE O^ PROJECT (80 cnamcmrt or m*s Titm mutt tit on on* ime Omrwen tn» Oorvn.) Assessment of the Size of the Leak Induced in Retinal Vessels Using PITC-Dextrans PRINCIPAL INVESTIGATOR (Lat otrmr pmttgtnnai ptrvxmai ouow tn» fnncffi mvtttiftof ) (Hmm* OM ttaorutorf. una rumui* tflmaooni PI: Alan G. Palestine M.D, Head, Section on Clinical Immunology LI, NEI Others: Susan Lightman M.D. Visiting Fellow LI, NEI COOPERATING UNITS (H any) Laboratory of Ophthalmic Pathology, National Eye Institute (Toichiro Kuwabara); Laboratory of Ophthalmic Pathology, National Eye Institute (Laura Caspers-Velu) LAB/BRANCH Laboratory of Immunology SECTION Section on Clinical Immunoloev INSTITUTE AND LOCATION NEI. NIH, Bethesda. Maryland 20892 TOTAL MAN- YEARS: 0.3 PROFESSIONAL: 0.3 OTHER; CHECK APPROPRIATE BOX(ES) O (a) Human subjects D (a1) Minors D (a2) interviews D (b) Human tissues IB (c) Neither SUMMARY Of WORK (Un ttmnow unrwouota typt Do not axCMO me xptca prow tn* Fniapt' inr»stigttor ) (Ntmt, ont moorttory tna rtinum trtmtoonj PI: Barbara Detrick Others: John J. Hooks Gerald J. Chader Merlyn Rodrigues Caroline Percopo Ph.D. Ph.D. Ph.D. M.D., Expert LI, NEI Ph.D. A.B. Head, Section on Immunology LI, NEI and Virology Chief LVR, NEI Head, Section on Clinical LOP, NEI Eye Pathology Biologist LI. NEI COOPERATING UNITS ^/r .ny; Walter Reed Army Medical Center, Washington, D.C. (Magda Tomaszewski, M.D.); Walter Reed Army Medical Center, Washington, D.C. (David Katz, M.D.); Duke University, Durham, North Carolina (Barton Haynes, M.D.); Ruprecht- Karl's U niversity. Heidelberg, CerTnany fFllen Kraiis-Markiw , K.D.) LAB/BRANCH Laborato ry nf TniTTinnnl iigX. SECTION Section on Immunoregulation INSTTTLTrE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 0.65 PROFESSIONAL: 0.A5 OTHER. 0.2 CHECK APPROPRIATE BOX/ES) El (a) Human subjects D (a1} Minors D {a2) Interviews D (b) Human tissues D (c) Neither SUMMARY OF WORK (Uu ttanowv imnauota rype. Oo nor •ZCM0 the tpaca pnxnote.) Class II antigens (HLA-DR and HLA-DQ) are membrane bound glycoproteins encoded by genes in the major histocompatibility complex. In addition to their well established role as regulatory molecules of the immune response, these determinants are now suspected of playing an influencial part in cellular differentiation . In exploring the cellular composition of a popular childhood tumor, retinoblastoma, we identified the presence of HLA-DR and HLA-DQ antigens on a population of undifferentiated malignant cells of the retina. This study provides the initial description of these class II antigens on retinoblastoma cells. Furthermore, HLA-DR antigen was found to be coexpressed on cells that contained both neuronal and glial markers. This study also identifies for the first time the presence of class II antigens on cells of neuronal origin. Based on these initial studies, additional investigations are in progress. One approach focuses on the possible role of class II antigens in cellular differentiation or immune reactivity. A second examines the prognostic significance of these molecules on retinoblastoma cells and the possible relationship class II proteins may have to the modulation and management of this tumor. Finally, a third study will examine the role of IFN-gamma as a differentiating agent of this tumor. C»0 1 1 «.•!• y'l-yr^fiw DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT JMUMBES ZOl EY 00232-02 LI PERIOD COVERED October 1, 1986 to September 30. 1987 TfTLE OF PROJECT (BO cft«r»cr»n or mts Tiut must Irt on one lint o»tw—n tne ooramri.) Interferon System in Cellular Function and m^P^^f^ PRINCIPAL INVESTIGATOR (Lat om»' pmtmuionti parionn»l tmow m* fnncieai Inmtigtmr I (Namt, m» lumeatoiy. ana ntoiutc aftmaoon) PI: John J, Hooks Ph.D. Others: Barbara Detrick Ph.D. Caroline Percopo A.B. Christian Hamel M.D. Muriel Kaiser-Kupfer M.D. Head, Section on Immunology LI, NEI and Virology Expert LI, NEI Biologist LI, NEI Visiting Fellow LI, NEI Head, Section on Ophthalmic CB, NEI COOPERATING UNITS (H any) Newjork University, School of Medicine, Department of Microbiology (Jan Vilcek, LAB«RANCH Laboratory of Immunology SECTION Section on Immunology and Virology INSTITUTE AND LOCATION NEI, NIH, Bethesda. Maryland 20892 TOTAL MAN- YEARS; 1.15 PROfESSIONAL; 0.75 OTHER. 0.4 CHECK APPROPRIATE BOX/ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues IS (c) Neither SUMMARY OF WORK (Uta sxanoara unrtauctO typa. Do not axc^aO the spaca promoaO.) The IFN proteins can modify a variety of biological activities and are considered one of the body's regulatory proteins. Numerous studies now indicate that the IFN's are potent immunoregulators. During the past year we have been studying the ways in which IFN proteins interact with cells of the immune system and how this interaction may modify immune responses and immunologically related disorders . Using immunocytochemical analysis we have developed a sensitive method of identifying lymphokines, IFN-gamma and IL2, at the site of tissue damage. We have identified the lymphokines, IFN-gamma and IL2 in inflammatory eye diseases. The presence of these lymphokines is associated with a lymphocyte infiltrate predominantly of a T-cell origin and with the expression of MHC class II antigens on both the infiltrating cells and in the retinal pigment epithelial (rpe) cells. This is the first demonstration of lymphokines, IFN-gamma and 112 at the site of a localized autoimmune disease. These observations may indicate that IFN-gamma induced MHC class II antigen expression may serve as a local amplification system in autoimmune and inflammatory eye disease. A better understanding of the role of lymphokines in the mechanisms involved in the development of autoimmunity and inflammation may be beneficial in the treatment of these diseases . PHS 6040 Ihev 1/M) DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT .\UMB£= ZOl EY 00233-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE Of PROJECT f$0 cnmrmawri or ou Tnm must tn on orm knt Omrw—n tn» Domn.) Studies on the Bioregulatory Aspects of the Retinal Pigment Epithelial Cell PRINCIPAL INVESTIGATOR (Lat otrmr profujonn persormn osfow tnm Pnnupti Intrmittgttor.) ISamt. OM. moortmry. ana ntmun arNwiw); PI: John J. Hooks Ph.D. Others: Barbara Detrick Ph.D. Caroline Percopo A.B. Susan Robbins Ph.D. Laura Caspers-Velu M.D. Head, Section on Immunology and Virology Expert Biologist Postdoctoral Fellow Visiting Associate LI, NEI LI, NEI LI, NEI LI, NEI LOP, NEI COOPERATING UNITS f/r«.w Hopital St. Louis, Paris, France (Lawrence Bowsell, M.D.); Institute Gustave Rowsse, Villjuif, France (Alain Bernard, M.D.); National Institute of Dental Research, Laboratory of Microbiology & Immunology (Reuben Siraganian, M.D.) LAB^ RANCH Laboratory of Immunology SECTION Section on Immunology and Virology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 1.A5 PROFESSIONAL 1.25 OTHER: 0.2 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) lnterviev« 13 (b) Human tissues D (c) Neither SUMMARY Of WORK (U$t ttanavc unrtoucmo typt Do not tieaee tne tpaca promote.) The retinal pigment epithelial (rpe) cell is a major regulatory cell in the eye. That is, the rpe cell exerts a variety of actions in maintaining retinal integrity and function. In order to more effectively study this cell in vivo and in vitro, we have produced monoclonal antibodies directed against human rpe cells. Using immunoperoxidase assays (ABC) , we have identified two mouse IgG monoclonal antibodies which react with the human rpe cell. The monoclonal antibodies are both specific for the rpe cell within the eye, since they do not react with any other ocular structures. Moreover, these antibodies do not cross react with human skin, kidney or peripheral mononuclear cells. This is the first monoclonal antibody which is directed solely at the human rpe cell. Further characterization and studies with this antibody should prove useful in the identification of rpe cells in situ and in vitro. Moreover, this immunoglobulin will allow us to probe the bioregulatory functions of the cell. -^ C I^Ott *•• » • DEPARTMENT OF HEALTH AND HUMAN SERVICE: • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT MuMBcS ZOl EY 0023A-02 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OP PROJECT (BO cnarucmn or •» Tm, mior tn on on* imt Dmtw—n trw ooroan.) MHC Class II Antigens in the Pathogenesis of Inflammatory Diseases PRINCIPAL INVESTIGATOR (Lat omur profunnti parxonnti o»io» an frmcipai Inrtsiigttor ) (Namt, on*, moorwtory. mna mmun aftikaoon) PI: John J. Hooks Ph.D. Others: Barbara Detrick Ph.D. Christian Hamel M.D. Chi-Chao Chan M.D. Robert B. Nussenblatt M.D. Head, Section on Immunology and Virology Expert Visiting Fellow Senior Staff Fellow Clinical Director LI, NEI LI, NEI LI, NEI LI, NEI NEI COOPERATING UNITS (K any) loannina School of Medicine, loannina, Greece (Haralampos M. Moulsopoulos, M.D.) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunology and Virology INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS; 0.65 PROFESSIONAL: 0.65 OTHER CHECK APPROPRIATE BOXfES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues El (c) Neither SUMMARY OF WORK (Uf gnnaarxi unraoooae typt Do not mxcte the uxca (nxnoaa.) MHC class II antigens, HLA-DR in the human and la in the mouse, are membrane bound glycoproteins that are encoded by genes of the major histocompatibility complex. Expression of these antigens is of great functional importance for the initiation and perpetuation of immune responses. In a number of immuno- pathologic conditions HLA-DR antigen negative cells are stimulated to express class II antigens. In these cases an immunologic role has been postulated for the class II antigen expression. During the past year, we have determined if class II antigens are expressed in certain diseases and we have evaluated their possible role in autoimmune and inflammatory diseases. Initial studies identified cells in the anterior segment and cells in the retina (rpe cell) which express class II antigens during inflammatory eye diseases. Treatment with monoclonal anti-la antibodies diminished the clinical disease and the expression of MHC class II antigens. These studies have been extended to evaluate Sjogren's syndrome. We found that the salivary gland in Sjogren's syndrome is infiltrated predominantly by T-lymphocytes and that this is associated with class II antigen expression on glandular epithelial cells. Moreover, we evaluated the effect of cyclosporin A on the immunopathological lesions in Sjogren's syndrome. We found that cyclosporin treatment resulted in a decrease in both T cell infiltration and a decrease in HLA-DR antigen expression. These studies on MHC class II antigen expression in localized autoimmune diseases provide evidence that the activation of these antigens may contribute to the immunopathogenesis of these disease. PHS 6040 (fiev 1/S41 C*0 (I*.*!! DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30, 1987 pROjEC' number ZOl EY 00235-02 LI TfTLE OF PROJECT (SO eft»f»ci»n or mi Tom musi tn or. on» un* t»iw»»n trw ooroft.) Identification and Modulation of Class II Antigens PRINCIPAL INVESTIGATOR (Lat omtr proltuionMi personrmi osotr m* PnnoDai Invwitigttoi I INtmt, tan mooratory. »na ratnim aftmaoon/ PI: Barbara Detrick Ph.D. Expert LI, NEI Others: John J. Hooks Richard Wetzig Chi-Chao Chan Caroline Percopo Robert B. Nussenblatt Ph.D. Head, Section on Immunology LI, NEI and Virology M.D. Senior Staff Fellow LI, NEI M.D. Senior Staff Fellow LI, NEI A.B. Biologist LI, NEI M.D.. Clinical Director NEI COOPERATING UNITS fA.ny; g^^ ^^^ ^^^ Infirmary, University of Illinois, Chicago, Illinois (M.O.M. Tso, M.D.); Duke University, Durham, North Carolina (Barton F. Haynes, M.D.); Paris, France (Laurence Boumsell, M.D.); and Paris, France (Alain Bernard, N.D.) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 0.A3 PROFESSIONAL; 0.33 OTHER. iLJ- CHECK APPROPRIATE BOX(ES) D (a) Human subjects O (a1) Minors □ (a2) Interviews D (b) Human tissues CB (c) Neither SUMMARY OF WORK (Utt ttmnatrv unntauc^O typt Do not cicmC tht tpac* provote.) Class II antigens are membrane bound glycoproteins encoded by genes in the mixed histocompatibility complex. Their expression is critical to immune reactivity. Although most immune cells constitutively express class II antigens, some non- immune cell types can be induced to demonstrate these molecules under selected conditions, such as an immunologic or degenerative event. Based on our earlier data, which demonstrated that retinitis pigmentosa patients had an alteration in IFN-gamma production and class II antigen expression and rpe cells can, in special instances, express class II antigens, we expanded our studies to evaluate class II antigen expression in a variety of ocular situations. We found that the rpe cell does not express class II antigen in the normal eye. In contrast, the rpe cell did express these molecules in a retinal degenerative disorder (retinitis pigmentosa) and in two ocular inflammatory diseases (sympa- thetic ophthalmia and uveitis) . Using the EAU animal model of ocular autoimmune disease we demonstrated that the rpe cell is activated to express class II antigens prior to clinical and histopathological evidence of the disease. Finally, we demonstrated that EAU could be altered with anti-la therapy. In this study EAU animals receiving monoclonal anti-la antibodies experience not only less ocular inflammation but also a delay in the onset of EAU. Moreover, immunocytochemistry analysis revealed that eyes from these animals expressed less la antigen as well as a diminution of infiltrating macrophages and lymphocytes. These data show that anti-la treatment significantly modifies the course of EAU in the rat. We are continuing to investigate the effects of other potent modulators such as IFN-gamma and cyclosporine on class II antigen expression with the hope that an alteration in activation or expression of these molecules may modify the disease process to the benefit of the host. c^^^^«j«ii DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT , PROJECT NUMBER Z01 EY 00237-02 LMOD PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (80 chtrtcttrs or toss TlOa must ht on ona lint butw—n tht borOtn.) Characterization of the Primate Lens PRINCIPAL INVESTIGATOR (List other prottssionai personnel below the Pnnapel Investigator ) (Name, title, laboratory, and msotute afhliaoon) PI: Paul Russell Ph.D. Research Chemist LMOD, NEI Others: Masao Nakamura M.D. Visiting Associate LMOD, NEI COOPERATING UNITS (» any) Division of Cancer Research, University of Toronto (S. L.-C. Tsui) Meakin, M. Breitman, LAB/BRANCH Laboratory of Mechanisms of Ocular Diseases SECTION Section on Cataract INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS; 1.7 PROFESSIONAL; 1.7 OTHER: 0.0 CHECK APPROPRIATE BOX(ES) n (a) Human subjects D (a1) Minors D (a2) Interviews [^ (b) Human tissues D (c) Neither SUMMARY OF WORK (Use standard unreduced type Do not enceed the apace provided.) The most prevalent proteins in the human lens are the crystallins. One of the major groups of these proteins are called gamma crystallins. Because of altera- tions in these crystallins upon aging in the lens and the difficulty in getting purified polypeptide, the protein sequences of these crystallins are not known. The nucleotide sequences of the "T-crystallin family are known, however. As an alternate approach for assigning these genes to specific polypeptides, the genes for three of the Y-crystallins were stably integrated into mouse L-cells, a fibroblast cell line. The products of these genes that were expressed in the fibroblasts could then be compared to the proteins found in the human lens. Three of the human gamma crystallins expressed in the mouse cells have been shown to have properties identical to the Y-crystallins found in the human lens. The aging of crystallins in vivo has been difficult to study because che exact mechanism for the alterations is not known. By using the Y-crystallins expressed in vitro in a mixed-function oxidation system, the microheterogeneity and shift to more acidic crystallin components found in the aging lens has been duplicated in vitro. In addition to the work on the Y-crystallins, studies with lens membrane have also been done. A major protein in the membrane fraction of cell lenses has been identified as calpactin I. This protein is known to associate with actin in the presence of calcium and phospholipid. This protein may play a major role in the process of differentiation of lens epithelium to lens fiber. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PERIOD COVERED October 1, 1986 to September 30, 1987 PROJECT NUMBER Z01 EY 00238-02 LMDB TITLE OF PROJECT (80 characters or less Title rrjust fit on one line between the borders ) Proto-oncogene Expression During Lens Differentiation and Development PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator ) (Name, title, laboratory, and institute affiliation) PI: Peggy Zelenka Ph.D. Geneticist LMDB, NEI Others: Luke Pallansch Howard Beswick Ph.D. Staff Fellow Ph.D. Visiting Fellow LMDB, NEI LMDB, NEI COOPERATING UNITS (if any) liana Keshet Ph.D. Visiting Fellow LMDB, NEI LAB/BRANCH Laboratory of Molecular and Developmental Biology SECTION INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS 2.3 PROFESSIONAL: 2.0 OTHER; 0.3 CHECK APPROPRIATE BOX(ES) D (a) Human subjects D (a1) Minors D (a2) Interviews D (b) Human tissues H (c) Neither SUMMARY OF WORK (Use standard unreduced Type Do not exceed the space provided.) This project investigates the expression of proto-oncogenes differentiation of embryonic lens epithelial cells to form 1 seeks to determine the specific function of the correspondin the developing lens. Using radioactively labeled DNA probes demonstrated that levels of c-myc mRNA are transiently eleva few hours after the initiation of differentiation in vitro, c-myc mRNA seems to be post-transcriptionally regulated, as small-scale nuclear run-on transcription assay developed in which allows measurements to be made on as few as 10° cells, lipoxygenase pathway of arachidonic acid metabolism produce of c-myc mRNA, which also seems to be post-transcriptionally Analysis of the arachidonic acid metabolites synthesized by epithelial explants has confirmed that elevated c-myc mRNA 1 with the disappearance of a specific lipoxygenase pathway me during the ens fiber cells, and g gene products in we have ted during the first The elevation of determined by a this laboratory. Inhibitors of the a similar elevation regulated. differentiating lens evels are correlated tabolite. DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PBOjECT MUM6ES ZOl EY 00239-01 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE Of PROJECT (90 cnarmcnn or wu T(K» mtat tn on ont mh 0mrw9»n irm Domn.) Penetrating Keratoplasty in the Rat PRINCIPAL INVESTIGATOR (Lai otnmr profttionti p»nonn»i t»iow mm Pnnapai mvwtiigator ) (N»m», oi». mooftoiy. mna msmut* anmaoon) PI: Edward J. Holland M.D. Senior Staff Fellow Others: Chi-Chao Chan M.D. Richard P. Wetzig M.D. Robert B. Nussenblatt M.D. Senior Staff Fellow Senior Staff Fellow Clinical Director LI, NEI LI, NEI LI, NEI NEI COOPERATING UNITS (K any) LAB/BRANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTITUTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN-YEARS: 0.38 PROFESSIONAL; 0.38 OTHER CHECK APPROPRIATE BOX^) D (a) Human subjects D (a1) Minors D (a2) Interviews O (b) Human tissues H (c) Neither SUMMARY OF WORK (U*t txmnotrV unr90ix»e ryt». Do not azcMcr me toac* piwate.) A rat penetrating keratoplasty model was developed to evaluate the corneal allograft rejection reaction. Using Brown Norway rats as donor for Lewis rats and by not removing sutures, a rejection rate of approximately 90% could be seen by the third week. Inflammation of the grafts could be seen in the second week followed by vascularization. Monoclonal antibodies to T-lymphocyte subsets and major histocompatibility complex (MHC) antigenic markers in the rat are now available which allow for the delineation of the acute corneal rejection reaction. C^O •! ««*1* OEPARTVENT OT HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT MUM6ES ZOl EY 00240-01 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE Of PROJECT (BO cnmrmctmn or mu Torn musi tn on ont ut* MrtvMn m* oofomn.) Virus Infections in the Eye PRINCIPAL INVESTIGATOR (La: otntr prvtatannti pertonnti o» DEPARTMENT OF HEALTH AND HUMAN SERVICES • PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PBOjECT NUM6ES ZOl EY 00241-01 LI PERIOD COVERED October 1, 1986 to September 30, 1987 TITLE OF PROJECT (BO cffrtcnrs or »ts. T?o» must tn 0.1 oo» imt Omtw—n mt ooromrz.) Iramunopathology of Ocular Diseases PRINCIPAL INVESTIGATOR (List otnur pmrtutonai p»rjonn»/ omjmt m* PnnaaH Invtsiigttor 1 (Nam», m». laoorttOfY. ana msmjt* tiruiaoai) PI: Chi-Chao Chan M,D. Senior Staff Fellow LI, NEI Others: Robert B. Nussenblatt M.D. Alan G. Palestine M.D. Edward J. Holland M.D. Clinical Director NEI Head, Section on Clinical LI, NEI Immunology Senior Staff Fellow LI, NEI COOPERATING UNITS ((f «nw Zhongshan Ophthalmic Center, Guangzhon, China (Winifred Mao, M.D.); University of Iowa (Jay H. Krachmer, M.D.); Georgetown University Center for Sight (Michael Lemp, M.D. and Garth Stevens, Jr., M.D.) LAB/a RANCH Laboratory of Immunology SECTION Section on Immunoregulation INSTrruTE AND LOCATION NEI, NIH, Bethesda, Maryland 20892 TOTAL MAN- YEARS: 1.52 PROFESSIONAL; 1.52 OTHER; CHECK APPROPRIATE BOX