Astrocyte Heterogeneity and Metabolic Reprogramming: Mechanisms Governing Retinal Ganglion Cell Damage in Glaucoma

Glaucoma, a leading cause of irreversible visual impairment, is driven by progressive retinal ganglion cell (RGC) degeneration. Emerging evidence highlights astrocytes as pivotal players in its pathogenesis, with their heterogeneity and pathological metabolic reprogramming profoundly impacting RGC survival. This review synthesizes current insights into astrocyte diversity and metabolic alterations during glaucoma-related RGC injury, emphasizing molecular mechanisms from proteomic studies. Key focuses include fatty acid metabolism, neuroinflammation, and signaling pathways that modulate astrocyte function and contribute to neurodegeneration. Despite advances, challenges remain-particularly in characterizing astrocyte subtypes and identifying actionable targets within astrocyte-mediated metabolic/inflammatory cascades. By unraveling the interplay between astrocyte heterogeneity, metabolic reprogramming, and RGC vulnerability, this review provides novel theoretical frameworks to inform targeted glaucoma therapies.