Cellular Senescence: An Emerging Player in the Pathogenesis of AMD

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in the aged population. The accumulation of abnormal extracellular drusen deposits between the retinal pigment epithelium (RPE) and Bruch's membrane is a significant driver of AMD pathology. Drusen deposition leads to the degeneration of RPE cells and, subsequently, photoreceptors, driving the disease to its advanced stages and ultimately resulting in complete vision loss. Although the exact mechanisms underlying the AMD pathogenesis are not fully understood, it is hypothesized that the disease begins with the dysfunction of the RPE, triggering the complement and pro-inflammatory cascade. Over the last decade, new findings have implicated the involvement of cellular senescence (CS) in the pathology of age-related disorders. Specifically for AMD, evidence suggests that the senescence of RPE cells may play a role in the pathogenesis of the disease. In this review, we discuss the potential role of senescence in the onset and progression of AMD and propose potential therapeutic interventions that could be developed by targeting senescence.

Keywords: Age-related macular degeneration (AMD); Aging; Cellular senescence; Drusen; Pathogenesis; Retina; Retinal pigment epithelium (RPE); Therapeutics.