The proposed research is concerned with an experimental study of corneal diseases. The main emphasis is: a) To investigate the pathogenesis of corneal vascularization. These studies will be based upon a systematic investigation of the biological properties of the cornea and those factors inducing vascularity, with particular attention to those of clinical significance. An attempt will be made to quantitate corneal vascularizaton in rodents in reproducible experimental models by digitizing images obtained from flat preparations of corneas with colloidal carbon filled blood vessels and by using radioactive microspheres that are known to lodge in the microvasculature in direct proportion to blood flow. An attempt will also be made to quantitate corneal neovascularization in living animals by using an image processor to digitize images created by blood vessels. Part of this research will evaluate the relative roles of the angiogenic effect of mediators of the inflammatory response as well as of cellular elements of the blood (polymorphonuclear leukocytes, lymphocytes, monocytes and platelets) and plasma constituents. To minimize individual host responses many experiments on corneal vascularization will be performed on inbred mice with the same genome. b) To study the ultrastructural, and biochemical characteristics and pathophysiological reactions of corneal diseases, especially those in which abnormal materials deposit in the cornea. It is hoped to integrate the ultrastructural, biochemical, and metabolic aspects of certain corneal diseases. Particular attention will be paid to glycosaminoglycans, proteoglycans, collagen, and other proteins in the corneal stroma. Special attention will be devoted to keratoconus and the corneal dystrophies, especially macular corneal dystrophy. The studies will involve state-of-the-art energy dispersive x-ray microanalytical and image processing equipment, cell and organ cultures, monoclonal antibodies, immunochemistry and sensitive biochemical analytical methods. A registry of known cases of macular corneal dystrophy will be maintained and a genealogic and clinicopathologic investigation will be performed on these cases. Selected communities with a high gene frequency for macular corneal dystrophy will be screened for early cases with a sensitive ELISA technique that can detect keratan sulfate in serum and other body fluids.
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