STUDIES OF THE BIOREGULATORY ASPECTS OF THE RETINAL PIGMENT EPITHELIAL CELL

视网膜色素上皮(RPE)细胞在 维持神经的结构和生理完整性 视网膜。它的结构和功能作用可能会发生变化 光感受器和视力的丧失。我们已经研究了RPE细胞 广泛地作为后部重要的免疫调节细胞 眼睛的极点。我们对RPE细胞的研究活动可以细分为 分为三类：正常细胞功能研究、细胞因子 相互作用和传染过程。我们已经隔离并传播 在体外培养RPE细胞，并已开发出针对 对抗人类RPE细胞。RPE表位是一个67 kDa的蛋白质， 与微粒体膜密切相关。一个cdna克隆已经被 分离出一种与任何其他序列不匹配的蛋白质的密码 在数据库里。我们正在使用这些技术和试剂来评估 RPE细胞的分子、生化和生物学特性。 细胞因子，如干扰素(干扰素)-γ和IL-2，是一组 特殊的荷尔蒙样蛋白，对 细胞发育和对多种细胞功能的影响。这 该项目专注于研究细胞因子相互作用的方式。 与免疫系统的细胞和眼睛中的细胞 微环境。我们已经证明，干扰素-伽马能增强MHC-I类、MHC II类和ICAM-1在人和大鼠RPE细胞上的表达。此外， 干扰素-γ激活的RPE细胞可以处理抗原并将其呈递给辅助细胞 T淋巴细胞。此外，促炎细胞因子IL-1和肿瘤坏死因子， 诱导人RPE细胞IL-6、IL-8mRNA和蛋白的表达。这些研究 提示细胞因子介导的RPE细胞活化可能是RPE细胞的基础 眼免疫成分和RPE细胞的一个重要方面 移植。 繁殖和移植RPE细胞的研究也在进行中 各种各样的动物。我们已经建立了移植物排斥反应模型 将人RPE细胞移植到大鼠视网膜。这些研究 证明免疫反应的细胞和体液两个方面 被激活以拒绝RPE细胞移植。这些研究提供了 评价RPE细胞中细胞因子和免疫反应性的框架 移植。

The retinal pigment epithelium (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 the 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. We have isolated and propagated RPE cells in vitro and have developed monoclonal antibodies directed against human RPE cells. The RPE epitope is a 67 kDa protein that is closely associated with the microsomal membrane. A cDNA clone has been isolated that codes for a protein that does not match any other sequences in the databases. We are using these techniques and reagents to evaluate molecular, biochemical, and biological properties of the RPE cells. Cytokines, such as interferon (IFN)-gamma and IL-2, are a group of specialized hormone-like proteins that 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. We have shown that IFN-gamma enhances MHC class I, MHC class II, and ICAM-1 expression on human and rat RPE cells. Furthermore, IFN-gamma activated RPE cells can process and present antigen to helper T lymphocytes. Moreover, the proinflammatory cytokines, IL-1 and TNF, induce IL-6 and IL-8 mRNA and proteins by human RPE cells. 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. Studies are also in progress to propagate and transplant RPE cells in various animals. We have established a graft rejection model by transplanting human RPE cells into the rat retina. These studies demonstrate that both cellular and humoral aspects of the immune response are activated to reject RPE cell transplants. These studies provide the framework to evaluate cytokines and immune reactivity in RPE cell transplantation.