The long-term objective is to explore the pathologic process and pathogenetic mechanisms of retinal photic injury by pathologic, morphometric, and biochemical techniques so that therapeutic measures may be developed. Initially, models of retinal photic injury in rats and cynomologus monkeys will be established so that retinal photic injury may be assessed qualitatively by light and electron microscopy and quantitatively by morphometric evaluation of the photoreceptor nuclei of the outer nuclear layer. The severity of the photic injury will also be evaluated by measuring the loss of rhodopsin. Three chemicals will be administered to rats initially, and to monkeys, subsequently, to evaluate their effect on retinal photic injury. Each chemical represents a class of compounds that primarily probes a proposed pathogenetic mechanism that may attenuate photic injury. These chemicals include 1) Beta-carotene, a scavenger of singlet oxygen; 2) dimethyl thiourea, a scavenger of hydroxyl radicals; and 3) desferrioxamine, a metal-chelating agent. To examine the pharmacokinetics and pharmacodynamics of these chemicals, we will study the following aspects: 1) the distribution of drugs in the retina in relationship to doses administered; 2) the dose-response curve and their ameliorative effect on retinal photic injury; and 3) the time at which the drug is administered before, during, or after photic injury. After the optimum dose and time and route of administration have been determined in the rat, each will be given to monkeys, and the effects of these chemicals on retinal photic injury will be examined by light and electron microscopy. Subsequently, drugs will be administered to rats and monkeys in different combinations to evaluate their possible additive effects in attenuating retinal photic injury. The ultimate goal is to develop therapeutic measures to mitigate chronic degeneration of the retina produced by mild photic insult.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY006761-01
Application #
3263361
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1986-12-05
Project End
1991-11-30
Budget Start
1986-12-05
Budget End
1987-11-30
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Buchi, E R; Lam, T T; Suvaizdis, I et al. (1994) Injuries induced by diffuse photodynamic action in retina and choroid of albino rats. Morphologic study of an experimental model. Retina 14:370-8
Lam, T T; Fu, J; Chu, R et al. (1994) Intravitreal delivery of ganciclovir in rabbits by transscleral iontophoresis. J Ocul Pharmacol 10:571-5
Li, J; Edward, D P; Lam, T T et al. (1993) Amelioration of retinal photic injury by a combination of flunarizine and dimethylthiourea. Exp Eye Res 56:71-8
Takahashi, K; Lam, T T; Edward, D P et al. (1992) Protective effects of flunarizine on ischemic injury in the rat retina. Arch Ophthalmol 110:862-70
Fu, J; Lam, T T; Tso, M O (1992) Dexamethasone ameliorates retinal photic injury in albino rats. Exp Eye Res 54:583-94
Rosner, M; Lam, T T; Tso, M O (1992) Therapeutic parameters of methylprednisolone treatment for retinal photic injury in a rat model. Res Commun Chem Pathol Pharmacol 77:299-311
Rosner, M; Lam, T T; Fu, J et al. (1992) Methylprednisolone ameliorates retinal photic injury in rats. Arch Ophthalmol 110:857-61
Shahinfar, S; Edward, D P; Tso, M O (1991) A pathologic study of photoreceptor cell death in retinal photic injury. Curr Eye Res 10:47-59
Buchi, E R; Suivaizdis, I; Fu, J (1991) Pressure-induced retinal ischemia in rats: an experimental model for quantitative study. Ophthalmologica 203:138-47
Michon, J J; Li, Z L; Shioura, N et al. (1991) A comparative study of methods of photoreceptor morphometry. Invest Ophthalmol Vis Sci 32:280-4

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