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Toll样受体(TLR)。TLRs是宿主抵御微生物病原体的天然免疫的重要组成部分。在RPE细胞中检测到TLR1、2、3、4和5的基因表达。此外，经TLR激活剂处理后，TLR2、3和4的蛋白表达增强。由于RPE细胞是RNA和DNA病毒的复制场所，我们进一步研究了这些细胞中的TLR3信号。我们发现，dsRNA的类似物Poly I：C与人RPE细胞上的TLR3结合，导致干扰素-β等细胞因子、趋化因子和黏附分子的产生。RPE细胞上存在多个TLR以及由此产生的RPE细胞中的TLR信号表明，这些分子可能在视网膜内的内源性和获得性免疫反应中发挥重要作用。

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.