A temporal single-cell atlas of the retina uncovers the dynamic transcriptomic landscape of sodium iodate-induced retinopathy in mice.

Retinal degeneration involves complex interactions among diverse cell types, yet the dynamic cellular responses and intercellular communication remain incompletely characterized. Here, we generated a temporal single-cell RNA sequencing atlas of the mouse retina following sodium iodate-induced oxidative injury to characterize cell type-specific trajectories and stage-dependent interactions. Our analysis identified a distinct inflammatory-reactive Müller glia subpopulation enriched for Il1r1, Tnfrsf1a, and C3, which exhibited early activation of TNF/NF-κB/MAPK signaling and later engagement in chemokine signaling, ECM-receptor interaction, and synaptic regulation. Photoreceptor profiling further revealed two rod subclusters with differential vulnerability, in which the more susceptible Rod1 subpopulation displayed marked downregulation of phototransduction genes and selective enrichment of tumor necrosis factor (TNF) signaling. Microglia exhibited early expansion and upregulation of inflammatory gene programs, including Il1b, Tnf, and Ccr2, while in vitro assays confirmed that conditioned medium from sodium iodate-activated microglia reduced photoreceptor viability. Together, we show a conceptual model in which sodium iodate-induced oxidative stress is associated with early microglial inflammation and subsequent glia-photoreceptor crosstalk, suggesting a potential pathway that may contribute to selective rod degeneration. This study provides a comprehensive resource for dissecting retinal degenerative mechanisms and highlights critical temporal windows for therapeutic intervention.