The long term objective of this project is to study the pathologic alterations and pathogenetic mechanisms of photochemical injury of the retina in two rat models and two monkey models so that the pathologic changes in these various animal models of photic injury can be compared with those of age-related macular degeneration in man, Specifically, the first rat model of photochemical injury was induced by continuous exposure of freely moving adult albino rats to green light for 24 hours at an energy level of 175 foot candles and is characterized by degeneration of photoreceptor cells and pigment epithelium. The second rat model is produced under identical conditions but on a schedule of 10 seconds on, 10 seconds off and is characterized by diffuse loss of photoreceptor cells but with preservation of pigment epithelium. A detailed pathologic study will be carried out comparing the acute injury, macrophagic response and chronic retinal degeneration between the two models. Furthermore, comparison of the pathogenetic mechanisms of these two models of photochemical injury will be examined, including age, body temperature, vitamin A deficiency and various cycles of intermittent exposure. Immunohistochemical study of the photoreceptor proteins in these two models will be studied by monoclonal or polyclonal antibodies. These include, antibodies against transducin (alpha subunit), transducin (beta-gamma subunit), cyclic GMP phosphodiesterase, arrestin, opsin and interphotoreceptor retinoid-binding protein. Two models of retinal photochemical injury in monkeys will be studied. The first model consists of continuous exposure of the retina to blue light of 440 nm, and a second model consists of intermittent exposure to the same light at the same retinal irradiance, but on a 4-second-on, 4-second-off schedule. The detailed pathologic changes in the retina between these two models will be examined as will be the effects of elevation of body temperature and variation of intermittent light schedule. Immunohistochemical study of the photoreceptor proteins of the rod and cone cells will also be examined with antibodies listed in the rat models, as well as specific antibodies to blue cone opsin and red/green cone opsin. Aging human maculas exhibiting drusen, atrophic macular degeneration, and disciform macular degeneration will be studied by immunohistochemistry for alteration of the photoreceptor proteins of both the rod and cone cells as listed above. Furthermore, we will continue to perform clinico-pathologic studies of various retinal diseases in humans and examine the changes in photoreceptor proteins in these eyes whenever possible. The ultimate goal of this research project is to delineate the relationship of various models of photic injury and the retinal degenerative diseases in humans.
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