The long term objective of this project is to understand the role that communication between retinal pigment epithelial (RPE) cells and photoreceptor cells plays in the normal renewal of photoreceptor disk membranes, and how renewal is affected by isolating the retina from the RPE. Several Important functions and metabolic processes of retinal photoreceptor cells depend upon the apposition of the retina with healthy RPE cells. Pronounced changes In the morphology and function of photoreceptor cells can be produced by Isolating the retina from the RPE or by dystrophies that affect RPE cells. The consequences of such changes in vivo may be irreversible, and the resulting loss of vision may be permanent. The etiology of changes produced in photoreceptors and RPE cells by retinal detachment from the RPE are not known. In an organ culture model, we find that isolating Xenopus retinas from the RPE results in aberrant morphogenesis of disk membranes. In contrast, disk assembly in co-cultured attached retinas is normal (as measured by several morphometric techniques).
The specific aims of this project are Intended to answer several questions about the critical role that apposition of the retina with the RPE may play in the regulation of disk membrane assembly and morphogenesis: 1) Are processes of cell metabolism, gene expression and protein synthesis in photoreceptors affected? 2) What basic cell biological mechanisms are modified by isolating retinas from the RPE to cause abnormal disk assembly and morphogenesis? 3) Are effects of Isolating cultured retinas from the RPE reversible, either by re-establishing contact with the RPE or by restoring levels of potential trophic factors normally found in the subretinal space?
