Apoptosis by Fas in Human Retinal Pigment Epithelium

人视网膜色素上皮中 Fas 引起的细胞凋亡

• 批准号: 6552485
• 负责人: SHUNAI JIANG
• 金额: $ 5.44万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-05 至 2004-01-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6552485
• 关键词: CD95 molecule; aging; apoptosis; blood chemistry; clinical research; cysteine endopeptidases; enzyme inhibitors; human subject; macular degeneration; mitochondrial disease /disorder; organ culture; oxidative stress; postdoctoral investigator; retinal pigment epithelium

DESCRIPTION (provided by applicant): The purpose of this research proposal is to test the hypothesis that Fas-mediated apoptosis contributes to the death of RPE cells in 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. The recently published results from AREDS have demonstrated that antioxidants vitamins and zinc significantly reduce risk of vision loss from ARMD, which has provided a strong evidence that oxidative stress plays an important role in ARMD. My study has shown that Fas ligand/Fas mediates apoptosis and oxidant-induced cell death in cultured human RPE (hRPE) cells. Changes in the intracellular and extracellular redox status regulate Fas-mediated apoptosis and modulate the susceptibility to oxidative injury in hRPE cells. The research in the extend year will determine 1) whether Fas pathway is responsible for oxidant-induced mitochondrial changes in hRPE, 2) whether there is a change of FasL in plasma and circulating blood cells between non-ARMD and ARMD subjects, 3) whether blood cells induced to express high FasL cause apoptosis in cultured hRPE cells. 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.

描述（由申请人提供）：本研究提案的目的是检验Fas介导的细胞凋亡导致ARMD中RPE细胞死亡的假设。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。最近发表的来自AREDS的结果表明，抗氧化剂维生素和锌可显著降低ARMD导致视力丧失的风险，这为氧化应激在ARMD中发挥重要作用提供了强有力的证据。我的研究表明，Fas配体/Fas介导的细胞凋亡和氧化诱导的细胞死亡在培养的人RPE（hRPE）细胞。细胞内和细胞外氧化还原状态的变化调节Fas介导的细胞凋亡，并调节hRPE细胞对氧化损伤的易感性。本研究将探讨Fas通路是否与氧化剂诱导的hRPE细胞线粒体结构改变有关; 2）非ARMD和ARMD患者血浆和循环血细胞中FasL的表达是否发生变化; 3）高表达FasL的血细胞是否引起培养的hRPE细胞凋亡。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。