{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:48Z","timestamp":1792787628214,"version":"4.5.0"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82201211"],"award-info":[{"award-number":["82201211"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82471109"],"award-info":[{"award-number":["82471109"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:p>\n                    Diabetic retinopathy features early glial stress and neurovascular dysfunction, yet M\u00fcller glial programs linking inflammatory cues to oxidative injury remain unclear. We identify a spatially clustered interferon-stimulated gene 15 (ISG15)\n                    <jats:sup>+<\/jats:sup>\n                    M\u00fcller glial subtype expanded in streptozotocin-induced diabetic mice. High glucose alone did not increase basal free ISG15 or detectable ISGylation (ISG15-dependent protein modification) in primary M\u00fcller glia, whereas conditioned medium from high glucose\u2013exposed microglia induced both, recapitulated by IFN-\u03b2 and attenuated by type I interferon receptor 1 inhibition. In vivo,\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    RNAscope signals were associated with microglia, retinal\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    expression increased in diabetic retinas, and microglial depletion reduced\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    expression and limited the expansion of ISG15\n                    <jats:sup>+<\/jats:sup>\n                    M\u00fcller glia. M\u00fcller glia\u2013specific\n                    <jats:italic>Isg15<\/jats:italic>\n                    deletion preserved blood\u2013retinal barrier integrity, reduced acellular capillaries and Evans blue leakage, and mitigated oxidative stress, lipid peroxidation, and glutathione redox imbalance. Loss of ISG15 or disruption of ISGylation blunted interferon-driven oxidative stress in M\u00fcller glia and reduced M\u00fcller glia\u2013conditioned medium\u2013dependent endothelial migration and tube formation. Mechanistically, IFN-\u03b2 promoted peroxiredoxin 6 (PRDX6) ISGylation and proteasome-dependent degradation without altering\n                    <jats:italic>Prdx6<\/jats:italic>\n                    transcripts. Thus, microglial IFN-\u03b2 promotes an ISG15\n                    <jats:sup>+<\/jats:sup>\n                    M\u00fcller glial subtype that compromises antioxidant defense and promotes early barrier injury in diabetic retinopathy.\n                  <\/jats:p>","DOI":"10.1172\/jci205800","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:54:47Z","timestamp":1792004087000},"source":"Crossref","is-referenced-by-count":0,"title":["ISG15+ M\u00fcller glial subtype contributes to early blood\u2013retinal barrier breakdown in diabetic retinopathy"],"prefix":"10.1172","volume":"136","author":[{"given":"Tian","family":"Niu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindan","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjia","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-025-00646-x"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2025.101357"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nri3787"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2014.10.005"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1110593"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7879-0"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-018-04209-7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.168945"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2025028"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111532"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v12.i7.939"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.11613\/BM.2020.030502"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-012-1360-5"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-015-0653-z"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1371-6"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-39"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16330"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2337\/db17-1034"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2337\/db22-0970"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M115.052183"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.621938"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2023.109645"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43711-3"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13393-x"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.720765"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.08.017"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/antiox7120172"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.424"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00263-1"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45044-1"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16191-y"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02197-w"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01315-6"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0192-4"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00337-2"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01437-w"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06111-5"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i14.2118"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2019-001145"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-01024-4"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70337"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103078"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab321"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11040617"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238727"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3791\/66237"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2337\/db20-0839"}],"container-title":["Journal 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