STUDIES OF THE BIOREGULATORY ASPECTS OF THE RETINAL PIGMENT EPITHELIAL CELL

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The retinal pigment epithelial (RPE) cell plays a basic role in maintaining he structural and physiological integrity of the neural retina. We have isola d and propagated RPE cells in vitro and have developed monoclonal antibodies directed against human RPE cells. The RPE epitope is a 67 kDa protein that is closely associated with the microsomal membrane. A complementary deoxyribonucleic acid (cDNA) clone has been isolated that codes for a prote that does not match any other sequences in the databases. We are using these techniques and reagents to evaluate molecular, biochemical, and biological properties of the RPE cells. We have propagated human RPE cells in vitro and evaluated their ability to respond to cytokine activation. Transforming growth factor - beta (TGF-beta) is a potent cytokine that modifies a variety of cellular functio . This cytokine has been identified within the retina. We found that TGF-beta induces gene expression and production of Heme oxygenase (HO-1). Since HO-1 is a protective agent against oxidative damage in an O2 rich environment, RPE production of this protein may protect the retina against oxidative damage. Studies are also in progress to propagate and transplant RPE cells in various animals. We have established a graft rejection model by transplanting human RPE cells into the rat retina. These studies demonstrate that both cellular and humoral aspects of the immune response are activated to reject RPE cell transplants. These studies provide the framework to evaluate cytokines and immune reactivity in RPE cell transplantation.