{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:44:10Z","timestamp":1792712650866,"version":"4.5.0"},"reference-count":75,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T00:00:00Z","timestamp":1721692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271043"],"award-info":[{"award-number":["32271043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171047"],"award-info":[{"award-number":["82171047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301215"],"award-info":[{"award-number":["82301215"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020441","name":"Shanghai Brain","doi-asserted-by":"publisher","award":["MajorProject (No.2018SHZDZX01)"],"award-info":[{"award-number":["MajorProject (No.2018SHZDZX01)"]}],"id":[{"id":"10.13039\/100020441","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA\u2010146 (miR\u2010146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR\u2010146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR\u2010146 family only miR\u2010146a\u20105p expression was upregulated in COH retinas. The upregulation of miR\u2010146a\u20105p was observed in the activated microglia and M\u00fcller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR\u2010146a\u20105p in COH retinas reduced the levels pro\u2010inflammatory cytokines and upregulated the levels of anti\u2010inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR\u2010146a\u20105p mimic increased the percentage of anti\u2010inflammatory phenotype in the activated BV2 microglia, while transfection of miR\u2010146a\u20105p inhibitor resulted in the opposite effects. Transfection of miR\u2010146a\u20105p mimic\/agomir inhibited the levels of interleukin\u20101 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF\u2010\u03baB subunit p65. Dual luciferase reporter gene assay confirmed that miR\u2010146a\u20105p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF\u2010\u03baB by SN50 in cultured microglia reversed the miR\u2010146a\u20105p inhibitor\u2010induced changes of inflammatory cytokines. In COH retinas, overexpression of miR\u2010146a\u20105p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR\u2010146a\u20105p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1\/TRAF6\/NF\u2010\u03baB signaling pathway in microglia.<\/jats:p>","DOI":"10.1002\/glia.24600","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T04:25:41Z","timestamp":1721708741000},"page":"2115-2141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<scp>MicroRNA<\/scp>\n                    \u2010146a\u20105p protects retinal ganglion cells through reducing neuroinflammation in experimental glaucoma"],"prefix":"10.1002","volume":"72","author":[{"given":"Han","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Kang","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital, NHC Key Laboratory of Myopia, Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Third Affiliated Hospital, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Ying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3948-2943","authenticated-orcid":false,"given":"Yanying","family":"Miao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing\u2010Huai","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University  Shanghai China"},{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital, NHC Key Laboratory of Myopia, Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2279-6885","authenticated-orcid":false,"given":"Zhongfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1496-12.2012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.20s20.100916"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17060842"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.01.020"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.47408"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02236-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104304"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11132002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.05.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.04.016"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00953-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.11.007"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.12.048"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2023.121997"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2020.4806"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02012-y"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107776"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.06.050"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02366-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2020.8180"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1291-12.2012"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0955-0674(97)80068-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.09.002"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.006"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101163"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1576-3"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93994"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02315-8"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.12659\/msm.917082"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2795-6"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108728"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00534-9"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5407"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110594"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.10.002"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01110"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2021.08.011"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2023.101169"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.06.010"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/mib.0000000000000654"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012409"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2957"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1998.0577"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1530\/jme-21-0019"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-020-01515-0"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2021.02.003"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2016.0131"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040065"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.03.064"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118387"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0509-7"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.202317"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605298103"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ncrna3030022"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(17)30621-6"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15480"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.360277"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7711"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02855-1"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24256"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2017.02.014"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.11.014"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-022-00833-w"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108041"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.10.005"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2023.02.031"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-01046-4"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105442"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102687"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02951-7"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202466"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24354"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24307"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.10.004"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T04:54:12Z","timestamp":1732078452000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.24600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,23]]},"references-count":75,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/glia.24600"],"URL":"https:\/\/doi.org\/10.1002\/glia.24600","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,23]]},"assertion":[{"value":"2024-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}