Abstract: Proper migration and formation of the astrocyte network are essential for retinal vasculature and visual function. However, the underlying mechanisms remain incompletely understood. In the present study, we identified protein virilizer homolog VIR-like m6A methyltransferase associated (VIRMA)—the core scaffolding protein of the N6-methyladenosine (m6A) methyltransferase complex—as a novel regulator of retinal astrocytes and visual function. We demonstrated that the conditional knockout of VIRMA in retinal astrocytes impaired microglia-mediated phagocytic clearance, leading to abnormal astrocyte accumulation during postnatal development. Notably, this disruption in cellular homeostasis preceded subsequent pathological vascular remodeling. Although initial retinal vascularization appeared normal in VIRMA-deficient mice, persistent vascular plexus instability developed, ultimately leading to vessel regression and irreversible visual impairment. Mechanistically, single-nucleus transcriptomic analysis revealed that the loss of VIRMA disrupted the expression of multiple m6A-modified genes that are involved in extracellular matrix organization and angiogenesis. These molecular changes were correlated with impaired astrocyte–endothelial cell communication and contributed to the breakdown of vascular homeostasis. Collectively, our study identifies VIRMA/m6A as a novel regulator of the developmental elimination of retinal astrocytes and the maintenance of neurovascular integrity. This research provides new insights into astrocyte-related retinopathies and highlights potential therapeutic targets for vascular-associated visual disorders.

Key words: astrocyte elimination, development, N⁶-methyladenosine (m⁶A), microglial phagocytosis, retina, single-nucleus RNA sequencing, vessel regression, VIR-like m⁶A methyltransferase associated (VIRMA), visual impairment