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Apoptotic retinal cell clearance relies on microglial efferocytosis, but the impact of aging on this process has not been fully elucidated. In this study, we aimed to shed light on this by using single\u2010cell RNA sequencing (sc\u2010RNA\u2010seq) to compare young and aged mouse retinal transcriptional profiles, in which 74,412 retinal cells from young and aged mice were classified into 10 transcriptionally distinct retinal cell types, and differentially expressed genes between young versus aged retinas were mainly associated with cellular senescence and apoptosis. Furthermore, ligand\u2013receptor interactions (e.g., AXL\u2010GAS6, MERTK\u2010GAS6) between microglia and other retinal cells were strengthened in aged, compared to young retinas. Additionally, among microglia, Subcluster 4 was found under partial clustering to be associated with efferocytosis, of which aged microglia had downregulated efferocytosis\u2010associated genes. The impact of aging on microglial efferocytosis was further verified in\u00a0vitro by doxorubicin (DOX)\u2010induced senescent BV2 microglia, and in\u00a0vivo by a retinal ischemia\/reperfusion (I\/R) injury mouse model. In\u00a0vitro, DOX\u2010treated BV2 microglia had significantly lowered efferocytosis, as well as efferocytosis\u2010related MerTK and Axl protein expression; this was also present in\u00a0vivo in aged retinas post\u2010I\/R injury, with increased co\u2010localization of ionized calcium\u2010binding adapter molecule 1<jats:sup>+<\/jats:sup> microglia with apoptotic retinal cells, along with reduced efferocytosis\u2010related protein expression. Overall, microglial efferocytosis of apoptotic cells decreased with aging, suggesting that modulating this process could serve as a possible therapeutic target for age\u2010related retinal diseases.<\/jats:p>","DOI":"10.1111\/acel.70097","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T21:29:13Z","timestamp":1747344553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Single\u2010Cell <scp>RNA<\/scp>\u2010Seq Reveals Aging\u2010Related Impairment of Microglial Efferocytosis Contributing to Apoptotic Cells Accumulation After Retinal Injury"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-6550","authenticated-orcid":false,"given":"Pan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Second Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Future Medical Laboratory The 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