Autophagy Dysfunction, Cellular Senescence, and Abnormal Immune-Inflammatory Responses in AMD: From Mechanisms to Therapeutic Potential

Figure 1

The relationship of RPE cell autophagy dysfunction, cellular senescence, and abnormal immune-inflammatory response in AMD. Oxidative stress, aging, DNA damage, and ultraviolet radiation can lead to RPE cell autophagy dysfunction, cellular senescence, and BRB destruction. Autophagy dysfunction results in the decreased clearance of RPE cells and increased intracellular residual corpuscles, which interferes with cell metabolism. Senescent RPE cells lead to cell dysfunction and promote the senescence of surrounding cells by secreting SASP. Moreover, SNCs are apoptosis resistant, failing to enter programmed cell death and aggregating instead. The destruction of the BRB could activate an abnormal immune-inflammatory response of the retina and lead to the release of PRRs and inflammasomes, the activation of immune cells and cytokines, and the activation of abnormalities of the complement system, which could further amplify the local inflammatory response. These factors interact with each other, causing lipofuscin deposition, drusen formation, RPE cell injury or atrophy, photoreceptor damage, choroid degeneration, and ultimately, loss of vision.