Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?

Figure 7

Senescence as a critical factor in AMD pathogenesis. In certain stress conditions, which can be induced by environmental or/and lifestyle factors in aging retina, a major fraction of RPE cells become senescent and are no longer able to regenerate damaged RPE cells, which leads to AMD. The senescence of RPE cells can result from an interplay between aging, autophagy, and DDR in stress conditions. This interplay is a kind of vicious cycle as impaired DNA damage response (DDR) can lead to an increased damage to biomolecules by ROS. Damage to biomolecules induces the degradation of organelles via mTOR-dependent autophagy. This may lead to aggravation of oxidative stress and cellular damage as well as continue to impair autophagy and antioxidant defense by altered TFEB (transcription factor E-box binding) and PGC-1α signaling and increased ROS generation.