DEGENERATION AND REGENERATION IN THE MAMMALIAN RETINA

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When the retina is separated (detached) from the overlying monolayer of retinal pigment epithelium (APE) experimentally or as a consequence of injury, degenerative and proliferative changes occur in specific retinal cell types. When the retina is reapposed (reattached) to the RPE surface, the photoreceptor-RPE interface undergoes a significant degree of cellular "remodeling". In these experiments the detachment/ reattachment model will be used in a range of investigations designed to enhance our understanding of the retina's cellular response to, and recovery from, injury. 1. The relationship between photoreceptor outer segment degeneration, regeneration, and the integrity of the interphotoreceptor matrix (IPM) will be studied using the experimental retinal detachment model. A combination of immunochemical and lectin cytochemical techniques will be used to assess changes in specific [PM domains and components, and their relationship to retinal recovery. 2. Members of the Integrin family of adhesion receptors mediate the attachment of cells to extracellular matrix molecules. Integrins have been implicated in RPE cell anchorage to Bruch's membrane, in retina-APE adhesion, and in vitreoretinal adherence. A.) Specific integrins will be identified at three key retinal locations: the photoreceptor-RPE interface, Bruch's membrane, and the vitreoretinal border. B.) Integrins expressed by RPE cells in vivo will be compared to those expressed by RPE cells at various stages of differentiation in vitro. C.) Changes in integrin types and levels of expression will be compared in the normal, detached, and reattached retinas. 3. Transforming growth factor-beta (TGF-B) and fibroblast growth factors (FGF) are known to be present in the retina, however their functions are unknown. We will examine the roles of these two factors in the context of experimental retinal detachment/reattachment. We will identify: A.) Cellular and extracellular sites within the normal retina where these factors are located; B.) Modifications in their levels and/or distributions in the detached and reattached retina; C.) The retinal cell types that have receptors for these molecules; and D.) The effect(s) of exogenous TGF-B on intraretinal proliferation and interphotoreceptor matrix biosynthesis in vivo.