We have established cultures of endothelial cells (EC) and pericytes from bovine retinal tissue which we will use in developing an in vitro model system for the study of retinal pathologies. The proposed studies will examine various aspects of the growth control and biochemistry of retinal capillary cells as they relate to the development of retrolental fibroplasia (RLF). RLF is a proliferative retinopathy of the newborn infant which is correlated with exposure to increased oxygen. The pathogenesis of RLF is complex but appears to occur in two stages. We will utilize the cultures of retinal vascular cells to investigate the involvement of retinal capillaries in these events. The first phase, or the vasoconstrictive stage, occurs during exposure to high oxygen and is characterized by degenerative changes in the capillary endothelium of the developing retinal vessels. The effects of altered oxygen on retinal EC will be investigated by studying the generation of superoxide radicals and the activity of specific enzymes that play a role in mediating the toxic effects of oxygen. The second phase, or the vasoproliferative stage, is associated with the return to room air and consists of uncontrolled capillary proliferation. This event will be studied by determining the effect of a retina-derived angiogenic factor (which I have recently isolated) on the proliferation and migration of the retinal capillary EC. Pericytes, which have been postulated to play a role in the control of capillary proliferation are absent in capillaries of immature retinas. We will investigate the role of interactions between EC and pericytes in retinal pathology by studying the effects of co-cultured pericytes and their secreted products on EC proliferation. Finally, having studied the effects of oxygen, the retina-derived angiogenic factor and pericyte interaction on these cells, we will extend our cultures to cells derived from retinal tissue at different stages of retinal vascular development. These studies may contribute to an understanding of the role of vascular development in the pathogenesis of RLF. Ultimately, we hope to determine the sequence of events that leads ot the development of pathologic neovascularization. By identifying the conditions, events and factors that contribute to retinal neovascularization, we may gain insight into the means for prevention and cure of the proliferative retinopathies associated with a variety of disease states in man.
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