This proposal aims at elucidating functional and structural relationships between the retinal pigment epithelium (RPE) and photoreceptors, particularly those relevant to adhesion between retina and RPE and to the physiologic control of subretinal fluid. We will study the metabolic and passive mechanisms of retinal attachment by peeling or otherwise separating the retina from RPE under a variety of experimental conditions, while monitoring the forces involved and the histologic consequences. This will include investigation of possible contributions by interphotoreceptor matrix components and cell adhesion molecules. We will study fluid transport across RPE and the control of subretinal fluid volume by making experimental non- rhegmatogenous detachments in the living eye and correlating physiologic, fluorophotometric, histological and electrophysiological data. We will develop models of related clinical disorders such as serous detachments, RPE detachments and chorio-retinal ischemia. Our primary experimental animal is the rabbit, but studies will be extended to cats and primates to provide more definitive models for the human eye. Our goals are to gain physiologic knowledge of the normal attachment and fluid transport processes within the eye and, through our models of clinical disease, to identify therapeutic modalities. This work is directly pertinent to the clinical conditions of retinal detachment (both rhegmatogenous and non-rhegmatogenous), vascular and inflammatory disease which may cause detachment, and some aspects of age-related macular degeneration. We hope to find non-surgical means of modifying retinal adhesivity, so that the risk of detachment could be minimized. We also hope to find means to enhancing the removal of subretinal fluid so that detachments could be more effectively treated and prevented. At a more basic level, these studies will help us to understand the function of RPE in supporting the retina, and thus to better understand the significance of RPE damage in ocular disorders.
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