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Glaucoma is the leading cause of irreversible blindness with complicated pathogenesis still to be understood, where neuroinflammation was reported to be critically involved in its both initiation and progression. Whether IL\u201017A takes part in the pathogenesis of glaucoma through interfering neuroinflammation due to its potent proinflammatory effect is still unknown. In the present study, we investigated the role of IL\u201017A in the pathological process of glaucoma neuropathy as well as its relationship with the predominant immune inflammation mediator microglia in retina, trying to elucidate the underlying mechanisms from the view of inflammation modulation. In our study, RNA sequencing was performed for the retinas of chronic ocular hypertension (COH) and control mice. Western blot, RT\u2010PCR, immunofluorescence, and ELISA were used to evaluate the microglial activation and proinflammatory cytokines release at conditioned levels of IL\u201017A, along with assessment of optic nerve integrity including retinal ganglion cells (RGCs) counting, axonal neurofilament quantification, and flash visual\u2010evoked potential (F\u2010VEP) examination. And the possibly involved signaling pathways were screened out to go through further validation in scenarios with conditioned IL\u201017A. Subsequently, IL\u201017A was found to be significantly upregulated in COH retina. Furthermore, suppression of IL\u201017A effectively diminished the loss of RGCs, improved axonal quality, and F\u2010VEP performance in COH mice. Mechanistically, IL\u201017A promoted microglial activation and proinflammatory cytokines release along with enhanced phenotypic conversion of activated microglia to M2\u2010type in early stage and to M1\u2010type in late stage in glaucomatous retinas. Microglia elimination decreased the proinflammatory factors secretion, enhanced the RGCs survival and axonal quality mediated by IL\u201017A. Furthermore, IL\u201017A\u2010induced the overactivation of microglia in glaucomatous condition was alleviated after blocking the p38 MAPK pathway. Taken together, IL\u201017A is involved in the regulation of retinal immune response and RGCs cell death in experimental glaucoma by essentially promoting retinal microglial activation via p38 MAPK signaling pathway. IL\u201017A dynamically regulates the phenotypic conversion of retinal microglia in experimental glaucoma partly depending on the duration of elevated intraocular pressure. Suppression of IL\u201017A contributes to alleviate glaucoma neuropathy and exhibits promising potential as an innovative target for therapeutic strategy in glaucoma.<\/jats:p>","DOI":"10.1096\/fj.202202056rr","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T06:19:51Z","timestamp":1683267591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<scp>Interleukin\u201017A<\/scp>\n                    modulates retinal inflammation by regulating microglial activation via the p38\n                    <scp>MAPK<\/scp>\n                    pathway in experimental glaucoma neuropathy"],"prefix":"10.1096","volume":"37","author":[{"given":"Junjue","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Ruijin Hospital Affiliated Medical School Shanghai Jiao Tong University  Shanghai 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