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.
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