APOPTOSIS BY FAS IN HUMAN RETINAL PIGMENT EPITHELIUM

人视网膜色素上皮中 FAS 导致的细胞凋亡

• 批准号: 6206961
• 负责人: SHUNAI JIANG
• 金额: $ 4.63万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6206961
• 关键词: CD95 molecule; aging; apoptosis; clinical research; human subject; macular degeneration; oxidative stress; retinal pigment epithelium

This research proposal focuses on the hypothesis that Fas- mediated apoptosis contributes to oxidative injury of human RPE (hRPE) and thereby could contribute to age-related macular degeneration (ARMD). Previous research has shown that loss of RPE is a pivotal early event in ARMD and circumstantial evidence indicates that oxidative mechanisms are involved. Recent studies from this research group have shown that oxidant-induced cell death in hRPE may involve 2 mechanisms, activation of mitochondria-mediated apoptosis and activation of Fas-mediated apoptosis. The proposed research will determine 1) whether activation of Fas is a principal mechanism acting upstream of mitochondria in oxidant-induced apoptosis in hRPE, 2) whether physiologic processes associated with aging potentiate cell death mediated by Fas in cultured hRPE and 3) whether there is a sufficient concentration and variation in human blood levels of FasL (sFasL in plasma and FasL in monocytes) to warrant clinical studies of the potential association between blood FasL and ARMD. Although the successful completion of these aims cannot be expected to establish a mechanism for ARMD, they will provide important information on the possibility that Fas-mediated apoptosis plays a central role in the disease process.

本研究计划关注Fas介导的细胞凋亡促进人RPE（hRPE）的氧化损伤，从而可能导致年龄相关性黄斑变性（ARMD）的假设。 先前的研究表明，RPE的丧失是ARMD的关键早期事件，间接证据表明氧化机制参与其中。 本课题组最近的研究表明，氧化剂诱导的hRPE细胞死亡可能涉及两种机制，激活Fas介导的凋亡和激活Fas介导的凋亡。 该研究将确定1）Fas的激活是否是在hRPE中氧化剂诱导的细胞凋亡中作用于线粒体上游的主要机制，2）与衰老相关的生理过程是否增强培养的hRPE中Fas介导的细胞死亡，以及3）人血液中FasL水平是否存在足够的浓度和变化（血浆中的sFasL和单核细胞中的FasL）来保证血液FasL和ARMD之间的潜在关联的临床研究。虽然这些目标的成功完成不能期望建立一个机制ARMD，他们将提供重要的信息，Fas介导的细胞凋亡的可能性，在疾病过程中发挥了核心作用。