Single cell RNA-seq identifies a unique microglia subtype associated with retinal degeneration

In many forms of retinal degenerative diseases in human, microglia relocate to and accumulate in the subretinal space. However, the roles of microglia in retinal degeneration are poorly understood. By leveraging single cell RNA-seq, we identified a distinct microglia subtype in the subretinal space. These microglia underwent transcriptional reprogramming characterized by reduced expression of homeostatic checkpoint genes and upregulation of injury-responsive genes. Importantly, this transition is associated with protection of the retinal pigment epithelium from damage caused by disease. Therefore, our data demonstrated microglial heterogeneity in retinal degeneration and may provide important implications for developing new strategies to prevent loss of vision. Overall design: Transcriptional profiling of Cx3cr1+ single cells from the mouse model of light-induced retinal degeneration with matched control, generated from single cell RNA-sequencing of over 10,000 cells.

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O'Koren EG, Yu C, Klingeborn M, Wong AYW, Prigge CL, Mathew R, Kalnitsky J, Msallam RA, Silvin A, Kay JN, Bowes Rickman C, Arshavsky VY, Ginhoux F, Merad M, Saban DR