Single Cell RNA Sequencing Analysis of Mouse Retina Identifies a Subpopulation of Muller Glia Involved in Retinal Recovery From Injury in the FCD-LIRD Model

PURPOSE: Although retinal light injury models have been useful in understanding aspects of retinal degeneration and retinal oxidative stress, information on retinal recovery from oxidative/photoinflammatory retinal injury is scarce. The fundus camera-delivered light-induced retinal degeneration model is a simple and reproducible retinal light injury model developed to recapitulate not only the retinal degeneration aspect, but also the retinal recovery from injury. In this study, we used the fundus camera-delivered light-induced retinal degeneration model to perform cell type-specific analyses of the acute and subacute retinal responses to light injury. METHODS: C57BL/6J eyes were collected before or after light injury (4 hours, 48 hours, and day 5). Retina samples were processed into single-cell suspensions. Droplet-based encapsulation of single cells was performed to generate libraries for sequencing. RESULTS: Gene expression analysis generated 23 clusters encompassing all known major retinal cell populations. Using unbiased analyses, we identified genes and pathways that were significantly altered in each cell type after light injury, including some cellular processes suggestive of activation of pathways for retinal recovery (e.g., synaptogenesis signaling, ephrin receptor signaling, and Reelin signaling in neurons). More importantly, our data show that a subpopulation of Muller glia cells may play an important role in the cellular recovery process. CONCLUSIONS: This work identifies acute and subacute cell type-specific responses to retinal photo-oxidative injury. A subpopulation of Muller glia seems to initiate the cellular recovery process. A better understanding of these responses may be helpful in identifying therapeutic approaches to minimize retinal damage and maximize recovery after exposure to injury.