Microglia in retinal diseases: From pathogenesis towards therapeutic strategies

Microglia, a widely dispersed cohort of immune cells in the retina, are intricately involved in a diverse range of pivotal biological processes, including inflammation, vascular development, complement activation, antigen presentation, and phagocytosis. Within the retinal milieu, microglia are crucial for the clearance of dead cells and cellular debris, release of anti-inflammatory agents, and orchestration of vascular network remodeling to maintain homeostasis. In addition, microglia are key mediators of neuroinflammation. Triggered by oxidative stress, elevated intraocular pressure, genetic anomalies, and immune dysregulation, microglia release numerous inflammatory cytokines, contributing to the pathogenesis of various retinal disorders. Recent studies on the ontogeny and broad functions of microglia in the retina have elucidated their characteristics during retinal development, homeostasis, and disease. Furthermore, therapeutic strategies that target microglia and their effector cytokines have been developed and shown positive results for some retinal diseases. Therefore, we systematically review the microglial ontogeny in the retina, elucidate their dual roles in retinal homeostasis and disease pathogenesis, and demonstrate microglia-based targeted therapeutic strategies for retinal diseases.