The long term goal of this proposal is to investigate the genetic mechanisms and microenvironmental factors regulating the survival and differentiated function of retinal neurons and photoreceptors. The strategy used is based on comparative analysis of the differentiated fate of chick embryo retinal precursor cells as they develop either within their normal microenvironment in vivo, or under experimentally-controlled conditions in dissociated cultures. Terminal mitosis of the cells is determined by combined thymidine autoradiography and bromodeoxyuridine immunocytochemistry, and cell differentiation in vivo and in vitro is characterized using a multidisciplinary approach including immunocytochemistry, in situ hybridization, Northern blot analysis and the polymerase chain reaction. The mechanisms that control the differentiation of retinal precursor cells as either rod or cone photoreceptors will be studied by investigating the expression of the genes for visual pigments and other photoreceptor-specific molecules in vivo. Other experiments are proposed to analyze the expression of the homeobox genes Pax6, Prox1, Chx10, and Brn3 in developing retinal cells in vivo and in vitro, and their overexpression in cultured retinal cells using retroviral vectors. These studies are expected to shed light on cellular and molecular mechanisms of normal retinal development and function, and to contribute to the search for therapeutic approaches for retinal degenerative disorders.
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