Applications of single-cell transcriptomics in glaucoma research: from the aqueous humor outflow pathway to retinal ganglion cell neurodegeneration

Glaucoma is the leading cause of irreversible blindness worldwide, driven by progressive retinal ganglion cell (RGC) degeneration. While genetic and environmental risk factors have been identified, the cell-type-specific mechanisms underlying pathogenesis remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) enables high-resolution analysis of cellular heterogeneity, developmental trajectories and intercellular communication networks. This review synthesizes recent scRNA-seq advances across two critical domains in glaucoma research: (1) aqueous humor outflow pathway (AHOP) physiology and pathology; (2) primary open-angle glaucoma (POAG) pathogenesis. We identify convergent themes, including mitochondrial dysfunction as a shared mechanism across subtypes, the central role of neuroinflammation in RGC degeneration, and the therapeutic potential of metabolic interventions. We further discuss challenges in translating animal models to human disease, integrating multi-species datasets, and resolving cell-type-specific susceptibility. Finally, we highlight emerging directions in spatial transcriptomics, multi-omics integration, and precision medicine.