The retinal pigment epithelium (RPE) cell plays a basic role in maintaining the structural and physiological integrity of the neural retina. Alterations in its structural and functional actions can result in the loss of photoreceptors and vision. We have studied the RPE cell extensively as an important immunoregulatory cell within the posterior pole of the eye. Our research activities on RPE cells can be subdivided into three categories: normal cell function studies, cytokine interactions, and infectious processes. We have isolated 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 cDNA clone has been isolated that codes for a protein 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. Cytokines, such as interferon (IFN)-gamma and IL-2, are a group of specialized hormone-like proteins that exert profound influences on cellular development and on a variety of cellular functions. This project has concentrated on studying the ways in which cytokines interact with cells of the immune system and with cells in the ocular microenvironment. We have shown that IFN-gamma enhances MHC class I, MHC class II, and ICAM-1 expression on human and rat RPE cells. Furthermore, IFN-gamma activated RPE cells can process and present antigen to helper T lymphocytes. Moreover, the proinflammatory cytokines, IL-1 and TNF, induce IL-6 and IL-8 mRNA and proteins by human RPE cells. These studies indicate that cytokine-mediated activation of RPE cells may be a basic component of ocular immunity and an important aspect of RPE cell transplantation. 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.
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