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The retinal ganglion cells (RGCs) and their axons cannot be regenerated once damaged. Therefore, reducing RGC damage is crucial to prevent blindness. Accordingly, we aimed to investigate the potential influence of the gut microbiota on RGC survival, as well as the associated action mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the effects of microbiota, specifically <jats:italic>Bifidobacterium<\/jats:italic>, on RGC. Optic nerve crush (ONC) was used as a model of optic nerve injury. Vancomycin and <jats:italic>Bifidobacterium<\/jats:italic> were orally administered to specific pathogen\u2010free (SPF) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Bifidobacterium<\/jats:italic> promoted RGC survival and optic nerve regeneration. The administration of <jats:italic>Bifidobacterium<\/jats:italic> inhibited microglia activation but promoted M\u00fcller cell activation, which was accompanied by the downregulation of inflammatory cytokines and upregulation of neurotrophic factors and retinal ERK\/Fos signaling pathway activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrates that <jats:italic>Bifidobacterium<\/jats:italic>\u2010induced changes in intestinal flora promote RGC survival. The protective effect of <jats:italic>Bifidobacterium<\/jats:italic> on RGC can be attributed to the inhibition of microglia activation and promotion of M\u00fcller cell activation and the secondary regulation of inflammatory and neurotrophic factors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14165","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T09:30:05Z","timestamp":1678959005000},"page":"146-160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>Bifidobacterium<\/i> promotes retinal ganglion cell survival by regulating the balance of retinal glial cells"],"prefix":"10.1111","volume":"29","author":[{"given":"Xiaohuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Eye Diseases  Shanghai 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