STUDIES OF THE BIOREGULATORY ASPECTS OF THE RETINAL PIGMENT EPITHELIAL CELL

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The 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 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. Cytokines, such as interferon (IFN)-gamma and IL-2, are a group of specialized hormone-like proteins which 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. 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. During the past year, we have studied the interactions of infectious agents with HRPE cells and the subsequent activation of cytokine gene expression. We found that cytomegalovirus (CMV) infection of HRPE cells results in the enhanced secretion of the cytokine, IL-6. Northern blot analysis showed enhanced mRNA levels suggesting activation at the transcriptional level. We have previously shown that the HRPE cell may serve as a source of IL-6 in the eye. IL-6 is a proinflammatory cytokine which can be detected within the vitreous during human diseases and can induce uveitis following IL-6 injection. The ability of CMV to trigger IL-6 gene expression and production in RPE cells may identify one of the ways that viruses promote ocular inflammation. Moreover, this mechanism of cytokine production by HRPE cells may be a site of future therapeutic strategies for ocular inflammation.