STUDIES OF THE BIOREGULATORY ASPECTS OF THE RETINAL PIGMENT EPITHELIAL CELL

RPE细胞在维持神经视网膜的结构和生理完整性方面起着基本的作用。其结构和功能的改变会导致光感受器和视力的丧失。我们对RPE细胞作为眼后极重要的免疫调节细胞进行了广泛的研究。我们对RPE细胞的研究活动可分为三类：正常细胞功能研究、细胞因子相互作用研究和感染过程研究。细胞因子，如干扰素-γ和IL-2，是一组特殊的激素样蛋白，对细胞发育和多种细胞功能产生深远的影响。该项目致力于研究细胞因子与免疫系统的细胞以及眼部微环境中的细胞相互作用的方式。这些研究表明，细胞因子介导的RPE细胞活化可能是眼免疫的一个基本组成部分，也是RPE细胞移植的一个重要方面。在过去的一年里，我们研究了感染性因素与hRPE细胞的相互作用以及随后细胞因子基因表达的激活。我们发现，巨细胞病毒(CMV)感染人RPE细胞后，细胞因子IL-6和生长因子GM-CSF的分泌增加。Northern印迹分析显示，mRNA水平增强，表明转录水平处于激活状态。CMV反义寡核苷酸可下调CMV诱导的细胞因子基因表达和蛋白合成。IL-6是一种促炎细胞因子，在人类疾病期间可在玻璃体内检测到，注射IL-6后可诱发葡萄膜炎。巨细胞病毒能够在RPE细胞中触发细胞因子和生长因子基因的表达和产生，这可能是病毒促进眼部炎症的途径之一。此外，hRPE细胞产生细胞因子的这种机制可能是未来治疗眼部炎症的策略之一。

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