Decorin Protects Retinal Pigment Epithelium Cells from Oxidative Stress and Apoptosis via AMPK‐mTOR‐Regulated Autophagy
Xinyi Xie, Duo Li, Yuqing Cui, Tianhua Xie, Jiping Cai, Yong Yao
Abstract
Age‐related macular degeneration (AMD) is the leading cause of irreversible visual loss among the elderly worldwide with unidentified pathogenesis and limited therapeutic options. Oxidative stress‐induced damage to the retinal pigment epithelium (RPE) is central in the development and progression of AMD. Decorin (DCN), a small leucine‐rich proteoglycan, possesses powerful antifibrotic, anti‐inflammatory, and antiangiogenic properties. DCN has also been reported to serve a cytoprotective role in various cell types, but its protective effects against H 2 O 2 ‐induced oxidative stress and apoptosis in ARPE‐19 cells remain unclear. In this study, we showed that DCN significantly attenuated the increase in cell viability loss, apoptosis rate, and reactive oxygen species (ROS) levels in ARPE‐19 cells induced by H 2 O 2 . Furthermore, DCN activated the AMPK/mTOR pathway to promote autophagy while genetic inhibition of autophagy‐related gene 5 (ATG5) hindered autophagic process and diminished the protective role of DCN against oxidative stress in ARPE‐19 cells. Collectively, these results suggest that DCN could protect RPE cells from H 2 O 2 ‐induced oxidative stress and apoptosis via autophagy promotion, thus providing the therapeutic potential for AMD prevention and treatment.