age-related retinopathy in nrf2-deficient mice与年龄有关的nrf2-deficient老鼠的视网膜病变.pdfVIP

Age-Related Retinopathy in NRF2-Deficient Mice 1. 1. 1 1 2 Zhenyang Zhao , Yan Chen , Jian Wang , Paul Sternberg , Michael L. Freeman , Hans E. 3 1 Grossniklaus , Jiyang Cai * 1Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 2 Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 3 Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States of America Abstract Background: Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD- like retinal pathology with aging and to explore the underlying mechanisms. Methods and Findings: Eyes of both wild type and Nrf22/ 2 mice were examined in vivo by fundus photography and electroretinography (ERG). Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf22/ 2 mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE). Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV) and sub-RPE deposition of inflammatory proteins were present in Nrf22/ 2 mice after 12 months. Accumulation of autophagy-related vacu