ANTIOXIDANT SYSTEMS AND AGE RELATED MACULAR DEGENERATION

描述（摘自申请人摘要）：本研究项目

DESCRIPTION (Adapted from the applicant's abstract): This research program focuses on the hypotheses that age-related macular degeneration (ARMD) can result from oxidative injury to the retinal pigment epithelium (RPE) and that glutathione (GSH) may protect the retina and RPE cells from ARMD-associated with oxidative injury. Previous work has shown that there is a shift in blood plasma redox status to a more oxidized state with aging, placing all tissues at risk for age-related diseases; there also appears to be a more oxidized redox state in patients' with more advanced ARMD. In vitro studies suggest that oxidative injury-induced apoptotic cell death in RPE cells may involve mitochondrial damage. Further, dietary inducers can stimulate increased GSH synthesis leading to elevated intracellular GSH, with concomitant increased protection against oxidative injury. In this project, the investigators propose to answer the following questions which will test their hypotheses: (1) how redox status is associated with ARMD; (2) what mechanism is involved in shifting GSH redox status to a more oxidized state that affects RPE cell function; (3) whether one can modulate GSH synthetic capacity in human RPE cells by controlling the rate-limiting enzyme for GSH synthesis; and (4) what mechanisms are involved in the redox regulation of apoptosis in cultured human RPE cells. Biochemical studies, including HPLC, viability studies, measures of RPE function, TUNEL assay and other assays for apoptosis, and assays for mitochondrial function, will evaluate human blood plasma samples, cultured human RPE cells, and experimental animals. These studies should increase our understanding of the pathogenesis of ARMD, while directly suggesting new treatment strategies.