Relationship between Oxidative Stress, Circadian Rhythms, and AMD

Figure 3

Schematic presentation of the macroautophagy process in aged retinal pigment epithelial (RPE) cells. Oxidative stress, (ROS), and hypoxia lead to protein damage and aggregation, which induces autophagy. The substrate (cargo) for autophagy is degraded by lysosomal acid hydrolases, including cathepsins D, B, and L, after the fusion of lysosomes and autophagosomes to form autolysosomes. Rab7, LAMP-2A, and SNARE 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 because lysosomal lipofuscin disturbs cathepsin activity and autophagy flux. Fusion mechanisms in the RPE cells are under investigation. From Blasiak et al. [132], with the permission of the authors.