Microglia dysfunction emerges as overlooked driver of age-related macular degeneration

Age-related macular degeneration (AMD) stands as the leading cause of irreversible central vision loss in older adults, and emerging research reveals that dysfunctional microglia—resident immune cells within the retina—play a central role in its progression. These cells, which normally clear lipids and cellular debris to maintain retinal homeostasis, become excessively reactive and senescent with age, producing chronic inflammation that accelerates both dry AMD (retinal pigment epithelium atrophy) and wet AMD (choroidal neovascularization). Researchers have identified that the TREM2 receptor, expressed on microglia and other myeloid macrophages, regulates critical processes including phagocytosis, lipid handling, cell migration, and inflammatory tone; in experimental models, activation of TREM2 pathways has demonstrated capacity to restrict lesion expansion and modulate neovascularization severity. The current translational challenge lies in clinically distinguishing resident microglia contributions from infiltrating macrophages, yet accumulating evidence opens the door to therapies targeting microglial function restoration—potentially reshaping treatment for age-related blindness in longevity-focused medicine.