Granzyme B in age-related macular degeneration: mechanistic insights and therapeutic perspectives

Granzyme B (GzmB), beyond its established role in corneal and conjunctival disease, is increasingly recognized in the retinal and choroidal distribution of several pathologies. GzmB targets tight-junction proteins (e.g., ZO-1, JAM-A) and extracellular proteins such as fibronectin and laminin within the retinal pigment epithelium (RPE) and Bruch's membrane, thereby disrupting the outer blood-retinal barrier and contributing to the pathogenesis of age-related macular degeneration (AMD) and Macular neovascularization (MNV). This mini review highlights recent mechanistic insights into how GzmB drives extracellular matrix breakdown, inflammation, and angiogenesis; summarizes experimental and clinical evidence supporting its role in AMD; and discusses emerging therapeutic approaches, limitations, and translational potential for targeted therapy.