Studies from a number of laboratories have suggested that peroxidation of photoreceptor cell lipids is associated with and may be causal in certain types of retinal degenerations. Experiments are proposed to test the hypothesis that lipid peroxidation is a significant factor in photoreceptor degeneration. Three research projects are presented: 1) A number of studies have shown that certain nutrients are essential for normal retinal structure and function. Among these are included selenium, vitamin E, vitamin C, zinc, and taurine. Since some of these nutrients have anti-oxidant properties, we are proposing that essential nutrient deficiency may make animals more susceptible to light damaage. 2) Several retinotoxic agents have been identified: iron, lipid hydroperoxides, lead, and adriamycin. We will determine if these agents are promotors of lipid peroxidation in the retina. 3) We will study the effects of lipid peroxidation on the function of the retina in vitro. A series of quantitative biochemical, electrophysiological, and morphological studies have been designed to address these objectives. Prior to light strett, the normal defense mechanisms of each animal will be evaluated. These include determination of levels of vitamin E, vitamin C, and taurine. Enzymes that protect against peroxidative damage include glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase, and superoxide dismutase. The steady state levels of lipid hydroperoxides and polyunsaturated fatty acids will also be determined in these membranes. Baseline values for retinal function (determined by electroretinography) and ultrastructure will be established prior to the onset of stress. Other animals will be subjected to constant illumination for periods of time up to five days. Susceptibility to light damage will be determined by the following objective criteria: Increase in lipid hydroperoxides and decrease in polyunsaturated fatty acids in isolated fod outer segment membranes, decrease in amplitudes of the a- and b- waves with electroretinogram or any alteration in threshold or implicit time, and quantitative morphomoetric analysis of drop-out of photoreceptor cells determined by counting outer nuclear layer nuclei as a function of retinal position. Taken together, these quantitative studies on biochemistry, structure, and function of the retina will provide valuable information regarding the effects of lipid peroxidation on retinal degeneration.
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