Endo-Lysosome Function in the Retinal Pigment Epithelium in Health and Disease

Abstract

Polarized cells such as the retinal pigment epithelium (RPE) have elaborate endo-lysosomal networks that enable them to carry out efficient trafficking and metabolism of proteins and lipids, which is crucial for maintaining cellular homeostasis. Once thought to be little more than garbage disposal systems, late endosomes and lysosomes are now being recognized as highly dynamic platforms for macromolecule sorting, signaling, and cholesterol metabolism. Aging and age-related diseases are characterized by decreased endo-lysosomal function, disturbed cholesterol metabolism, and increased accumulation of lipid–protein aggregates called lipofuscin in postmitotic cells such as neurons and the RPE. Cholesterol accumulation and impaired endo-lysosomal function have emerged as key players in Alzheimer’s and Parkinson’s diseases. This review focuses on recent data supporting a link between endo-lysosome dysfunction, lipofuscin accumulation, and abnormal cholesterol homeostasis in the pathogenesis of age-related macular degeneration (AMD).