The proposed study is an investigation of the regional susceptibility and age dependency of photoreceptor cells to degeneration. Photoreceptor-specific degeneration will be produced in rats by three procedures, namely: constant light exposure, intravitreal injection of ferrous sulfate, and intraperitoneal injection of adriamycin. Initial experimentation will delineate the time course of photoreceptor loss using light microscope and electroretinographic examination. Concomitantly, light microscopy will be utilized to determine the regional distribution of degeneration throughout the entire retina (i.e., inferior, superior, nasal and temporal quadrants). In subsequent experiments, the susceptibility to photoreceptor degeneration will be compared between different age-groups of rats ranging from pre-pubescent (4 - 5 weeks) to old (greater than 18 months). Preliminary results show that in rats, photoreceptor susceptibility to degeneration increases with age and is greater in the superior versus the inferior retina. One long term objective of this project is to conduct assays for certain enzymes and antioxidants in the retina which protect against photoreceptor degeneration, and to compare their activities between retinal regions and in different age groups of rats. The protective agents to be assayed will include superoxide dismutase, catalase, glutathione peroxidase and vitamin E. The premise that these biochemicals can protect against photoreceptor degeneration is based on accumulating evidence that the peroxidation of membrane lipids is directly involved in photoreceptor destruction. The hypothesis to be tested is that differences in the susceptibility to photoreceptor degeneration which occur between retinal regions and with age are due to the increased (or decreased) levels or activities of enzymes and antioxidants in the retina which protect against lipid peroxidation. To summarize, the aim of the proposed research is to investigate factors which influence the susceptibility of the retina to experimental photoreceptor degenerations. These experiments could provide a better understanding of the mechanisms which are involved in causing and protecting against photoreceptor degeneration. Furthermore, this information could be helpful in devising preventative measures against photoreceptor degenerations in humans which arise from certain drug treatments and exposure to environmental retinotoxins.
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