This project will determine whether changes in the eye are correlated with visual impairment and cognitive decline in monkeys at known risk for cerebrovascular disease from hypertension and atherosclerosis. We will determine whether retinal changes such as microinfarction and hemorrhages indicate similar damage in the brain. In collaboration with Project 1, we will investigate the effect that such retinal pathology has on visual acuity and contrast sensititively. Clinical changes will be assessed at 6 weeks post-u[ (in short term animals) and followed for 12 or 48 months by color fundus photography and fluorescein angiography in the remaining animals. MRI scan of the vitreous following intravenous gadolinium infusion will provide a quantitative measure of the overall integrity of the blood-retina barrier at each examination interval. Anatomical experiments different types of damage. The functional, clinical and anatomical evaluation of the retina in this project will be correlated wit the cognitive, immunologic and neuropathologic changes detected in the same animals by the other projects. We will ask: 1) How are clinical changes in the retina correlated with the cognitive decline observed in the same animals? Is the animals's vision affected by these changes? Does observation of the retinal vasculature provide a "window" for changes that are occurring in the brain? 2) Are retinal ganglion cells injured by hypertension? Is this process exacerbated by an atherogenic diet? Do changes in synaptophysin labeling in the plexiform layers precede frank cell loss? 3) What effect do these two conditions have on the retinal interneurons and glia- the amacrine and Muller cells? Does the physical location of a cell or the fact that it has an axon affect the way it responds to the stresses imposed by these conditions? Do retinal glia (Muller cells) in damaged areas alter their expression of intermediated filaments or respond globally to damage? For all cell types local cell density will be determined using immunohistochemistry, and classic signs of cell damage will be documented. Clinical records will dictate the regions of the retinas we investigate in detail. In each retina, areas with different types of damage will be compared to undamaged areas. Clinical assessment of the fundus will be serial, so the same analysis can be performed on regions of the retina in which early signs of damage have disappeared by the time of sacrifice. Finally, the mechanisms that may protect the retina from temporary ischemia will be explored. Specifically, do retinal neurons responds to hypoxic stress by producing so-called "stress proteins" (e.g. the 72kD heat shock protein), or by activating "immediate early genes" (fos and jun)? Are specific growth factors induced in the retina in response to damage?