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The retinal microglia become activated in numerous pathological conditions, but the molecular signatures of these changes are poorly understood. Here, using an approach based on FACS and RNA\u2010seq, we show that microglial gene expression patterns gradually change during RGC degeneration induced by optic nerve injury. Most importantly, we found that the microglial cells strongly expressed <jats:italic>Tnf<\/jats:italic> and <jats:italic>Il1\u03b1<\/jats:italic>, both of which are known to induce neurotoxic reactive astrocytes, and were characterized by <jats:italic>Gpr84<\/jats:italic><jats:sup>high<\/jats:sup>\u2010expressing cells in a particular subpopulation. Moreover, ripasudil, a Rho kinase inhibitor, significantly blunted <jats:italic>Gpr84<\/jats:italic> expression and cytokine induction in vitro and in vivo. Finally, GPR84\u2010deficient mice prevented RGC loss in optic nerve\u2010injured retina. These results reveal that Rho kinase\u2010mediated GPR84 alteration strongly contribute to microglial activation and promote neurotoxicity, suggesting that Rho\u2010ROCK and GPR84 signaling may be potential therapeutic targets to prevent the neurotoxic microglial phenotype induced by optic nerve damage, such as occurs in traumatic optic neuropathy and glaucoma.<\/jats:p>","DOI":"10.1002\/glia.24442","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T09:25:11Z","timestamp":1689845111000},"page":"2609-2622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The <scp>GPR84<\/scp> molecule is a mediator of a subpopulation of retinal microglia that promote <scp>TNF<\/scp>\/<scp>IL<\/scp>\u20101\u03b1 expression via the <scp>rho\u2010ROCK<\/scp> pathway after optic nerve 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