Studies Of The Bioregulatory Aspects Of The Retinal Pigm

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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 Toll-Like receptors (TLR). TLRs are crucial components of innate immunity for host defense against microbial pathogens. Gene expression for TLR 1,2,3,4 and 5 was detected in RPE cells. Moreover, protein expression for TLR 2,3 and 4 was augmented by treatment with TLR activators. Because the RPE cell is a site of replication for both RNA and DNA viruses, we further investigated TLR 3 signaling in these cells We discovered that the binding of poly I:C, an analog of dsRNA, to TLR 3 on human RPE cells resulted in the production of IFN-beta and other cytokines, chemokines and adhesion molecules. The presence of several TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these molecules may play an important role in innante and adaptive immune responses within the retina.