The choriocapillaris, Bruch's membrane (BM) and retinal pigment epithelium (RPE) supply the major fraction of nutrients required by the photoreceptors and other cells of the outer neural retina. A knowledge of the basic properties of these structures is vital to the understanding of normal eye function and the pathogenesis of ocular dysfunction in conditions such as senile macular degeneration, uveitis, and neovascularization. Previous studies by the principal investigator have furnished a significant amount of this basic information including the permeability characteristics and surface properties of the choriocapillary endothelium, the proteoglycan components of BM, and the cell-surface molecules on the RPE. In the current proposal, this knowledge is applied to the study of the choriocapillaris and BM. In experimental models of uveitis, the permeability properties of the choriocapillaris will be examined to determine if alterations from the normal restriction to circulating plasma proteins exists prior to, and after, the onset of inflammation. Changes in the anionic moieties of BM following the infiltration of inflammatory cells will also be examined. These changes in the choriocapillaris and BM may potentiate the pathology seen in uveitis. Since histamine, a known vasoactive agent, is involved in the establishment of uveitis, a study of the possible ultrastructural localization of histamine receptors on the vascular endothelium will be done. Non-anticoagulant heparin and cortisone administration have been shown to inhibit the neovascularization of tumors in experimental models. This treatment will be applied to rats to determine if it is effective in the prevention of choroidal neovascularization seen after phototoxic injury. Additional studies will focus on the basic endothelial cell biology important to eye function. These are the choriocapillary endothelial pathways for the transit of retinol-carrier molecules bound for the RPE, the role of retinol in endothelial cell metabolism, and the nature of receptors for glycoproteins on the cell surface. These will be examined by ultrastructural cytochemical methods and will further lead to the understanding of the function of the choriocapillaris in normal and disease processes.
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