The direction of this grant has been and will be to undertake clinical, physiologic, pathologic, histochemical and biochemical studies of human retinal diseases and to create comparable animal models so that pathologic, pathogenetic and therapeutic investigations may be explored. I. In the coming grant period, we shall evaluate the hypothesis, that vitamin C plays an important role in ameliorating photic injury of the retina as a superoxide radical scavenger. We propose to examine the distribution of reduced and oxidized ascorbates in the neural retina and RPE-choroid complex in normal guinea pig, monkey and surgically enucleated and autopsy human eyes. The pathologic alterations of the normal and scorbutic retinas after photic injury will be studied. The effect of vitamin C on its withdrawal on retinal photic injury will be studied. II. We shall explore the model of experimental disciform macular degeneration with sub-RPE neovascularization in monkey, developed after exposure to the light of an indirect ophthalmoscope. Repeated short light exposures will be given to stimulate the sub-RPE neovascularization. Systemic hypertension will be induced to examine the response of sub-RPE neovascularization to this vascular disturbance. III. We shall continue to obtain human eyes with drusen, senile choroidal sclerosis, senile macular degeneration, cystoid macular edema, diabetic retinopathy, sickle cell retinopathy and other retinopathies and choroidopathies for detail studies utilizing the latest clinical, physiologic, pathologic, histochemical and biochemical techniques so that preventive and therapeutic measures for our patients may be designed. In the investigation of the above human diseases and animal models, the clinical course will be studied by fundus photography and fluorescein angiography; the disruption of the blood-retinal barrier by vitreous fluorophotometry and horseradish peroxidase tracer technique; the pathologic changes by light and electron microscopy; the alterations of the interphotoreceptor matrix and cyclic-GMP phosphodiesterase by histochemical techniques, and the changes of the oxidized and reduced ascorbates in the neural retina and RPE-choroid complex by biochemical analysis.
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