Studies Of The Bioregulatory Aspects Of The Retinal Pigm

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作用。其结构和功能作用的改变可导致光感受器和视力的丧失。我们已经广泛地研究了RPE细胞作为眼后极内的重要免疫调节细胞。我们对RPE细胞的研究活动可以分为三类：正常细胞功能研究，细胞因子相互作用和感染过程。细胞因子，如干扰素（IFN）-γ和IL-2，是一组专门的类胡萝卜素蛋白质，对细胞发育和各种细胞功能产生深远的影响。该项目集中于研究细胞因子与免疫系统细胞和眼部微环境细胞相互作用的方式。这些研究表明，甜菜碱介导的RPE细胞活化可能是眼免疫的基本组成部分，也是RPE细胞移植的重要方面。在过去的一年中，我们研究了HRPE细胞中细胞因子和环氧合酶基因表达的相互作用。环氧化酶（考克斯-2）表达的增加已在体内被发现与炎症、类风湿性关节炎、局部缺血和各种癌症相关。在这项研究中，我们表明，考克斯-2和它的产品，洋地黄素，产生时，人RPE细胞暴露于炎症细胞因子。NF-kB信号通路在此过程中起一定作用。此外，考克斯抑制剂，NSAIDS，显着降低考克斯-2基因表达和前列腺素的生产。这些研究表明，RPE细胞可能通过诱导考克斯-2参与正常和病理性视网膜疾病，并为免疫介导的视网膜病理学提供了新的治疗方法。

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 cytokines and cyclooxygenase gene expression in HRPE cells. Increases in cyclooxygenase (COX-2) expression has been found in vivo associated with inflammation, rheumatoid arthritis, ischemia and various cancers. In this study we showed that COX-2 and its products, prostaglandins, were produced when human RPE cells were exposed to inflammatory cytokines. NF-kB signaling pathway played a role in this process. Furthermore, COX inhibitors, NSAIDS, significantly decreased COX-2 gene expression and prostaglandin production. These studies indicate that RPE cells may participate in normal and pathologic retinal conditions through the induction of COX-2 and suggest novel therapeutic approaches for immune-mediated retinal pathology.