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础作用。其结构和功能的改变可导致光感受器和视力的丧失。RPE细胞作为眼后极内一种重要的免疫调节细胞，我们进行了广泛的研究。我们对RPE细胞的研究可分为三大类：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(IFN)- γ和IL-2，是一组特殊的激素样蛋白，对细胞发育和各种细胞功能产生深远影响。本项目主要研究细胞因子与免疫系统细胞和眼微环境细胞相互作用的途径。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）。tlr是一个先天免疫识别受体家族，可识别与微生物病原体相关的分子模式。细胞与TLR的反应性可诱导抗微生物免疫反应。我们研究并比较了TLRs在HRPE和人单核细胞中的基因表达和细胞质蛋白水平（U937）。在HRPE中检测TLR 1、2、3、4、5和9的基础表达水平。ifn - γ和LPS处理后，HRPE细胞中TLR基因表达和蛋白水平均有所提高。TLRs在HRPE和U937细胞中的不同表达模式表明视网膜细胞和单核细胞对微生物产物的反应不同。ifn - γ在炎症和感染性疾病中升高，可以上调HRPE中的选择性tlr，从而可能参与免疫致病过程。

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 a family of innate immune recognition receptors that recognize molecular patterns associated with microbial pathogens. Reactivity with the TLR on a cell induces antimicrobial immune responses. We investigated and compared the gene expression and cytoplasmic protein levels of TLRs in HRPE and in human monocyte cells (U937). Basal levels of TLR gene expression in HRPE was detected for TLR 1,2,3,4,5,and 9. TLR gene expression and protein levels were enhanced in HRPE cells treated with IFN-gamma and LPS. The differential patterns of expression of TLRs in HRPE and U937 cells suggest that retinal cells and monocytes respond differentially to microbial products. IFN-gamma, elevated during inflammatory and infectious diseases, can up regulate selective TLRs in HRPE and may thereby participate in immunopathogenic processes.