Autophagy and mitophagy in age-related macular degeneration: Custodians of retinal longevity

Age-related macular degeneration (AMD), primarily driven by dysfunction of the retinal pigment epithelium (RPE), is the leading cause of irreversible blindness in the elderly. As the central hub for photoreceptor support, nutrient transport, and waste clearance, the RPE is particularly vulnerable to age-related stressors that disrupt proteostasis and mitochondrial quality control. Autophagy and mitophagy are essential regulators of RPE and retinal longevity, ensuring the turnover of damaged proteins and organelles while maintaining energy homeostasis. In AMD, these pathways become compromised, contributing to lipofuscin accumulation, oxidative stress, inflammation, and progressive cell death. This review examines the physiological roles of autophagy and mitophagy in retinal homeostasis, their dysregulation in AMD, and emerging therapeutic approaches aimed at restoring these protective processes. Targeting autophagy and mitophagy is a promising strategy to preserve vision and delay the progression of AMD.