Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

Figure 2

Schematic presentation of the macroautophagy process in aged retinal pigment epithelial (RPE) cells. Oxidative stress, ROS, and hypoxia lead to protein damages and aggregation that induces autophagy. The substrate (cargo) for autophagy is degraded by lysosomal acid hydrolases, including cathepsins D, B, and L, after the fusion of lysosome and autophagosome that form autolysosome. Rab7, LAMP-2A, and SNAREs proteins are critical for the lysosome and autophagosome fusion process. Ubiquitin (Ub), LC3II, and p62 are complexed to the cargo and connect autophagy to the proteasomal clearance system. Macroautophagy is prevented in AMD, since lysosomal lipofuscin disturbs cathepsin activity and autophagy flux. Fusion mechanisms in the RPE cells are under investigation.