RPE Senescence and Its Implication in Age-Related Macular Degeneration

Cellular senescence is stable cell cycle arrest in response to replicative stress or other stresses. Cellular senescence is triggered by DNA damage and persistent DNA damage response, and is associated with metabolic reprogramming, chromatin rearrangement, and autophagy modulation. Senescent cells produce and secrete a combination of factors to exert non-cell-autonomous effects, referred to as senescence-associated secretory phenotype (SASP). Accumulation of senescent cells could drive aging and age-related diseases. Elimination of senescent cells using senolytic cocktail has been shown to reduce aging-associated phenotypes in mice. Age-related macular degeneration (AMD)Age-related macular degeneration (AMD) is the leading cause of irreversible blindness characterized by choroidal neovascularization, and loss of photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris (CC) at the advanced stage. RPE of the retina is essential for retinal homeostasis by functioning as the outer blood-retinal barrier and transporting nutrients/waste for the retinal photoreceptor cells. It functions as the first line of defense of the retina, and the phenotypic changes in RPE is believed to be the initial trigger for AMD. The mechanism of RPE degeneration and whether RPE senescence drives AMD progression is still unknown. In this book chapter, the mechanisms of cellular senescence as well as genetic and stress-induced models of RPE senescence will be summarized. The implication of RPE senescence in AMD will be discussed, and potential senescence-based AMD therapeutics will be outlined.