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 and the growth factor, GM-CSF. Northern blot analysis showed enhanced mRNA levels suggesting activation at the transcriptional level. CMV induced cytokine gene expression and protein production were down-regulated by CMV anti-sense oligonucleotide treatment. 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 cytokine and growth factor 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
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