{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:28:16Z","timestamp":1787329696336,"version":"build-2736575974"},"reference-count":49,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82260209"],"award-info":[{"award-number":["82260209"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation Key Program of Jiangxi Province","award":["20224ACB206021"],"award-info":[{"award-number":["20224ACB206021"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Diabetic retinopathy (DR) is one of the most common complications of diabetes worldwide and is associated with visual loss and blindness. However, effective treatments for both early- and late-stage DR remain lacking. A streptozotocin-induced diabetic mouse model and high glucose (HG)\u2013treated M\u00fcller cell model were established. M1\/M2 microglia polarization was assessed by immunofluorescence staining and flow cytometry. Expression of long noncoding RNA (lncRNA) OGRU, cytokines, and other key molecules was detected by quantitative RT-PCR or Western blot. ELISA was used to monitor cytokine secretion. M\u00fcller cell\u2013derived exosomes were isolated and characterized by nanopartical tracking analysis, Western blot, and transmission electron microscopy, and exosome uptake assay was used to monitor the intercellular transport of exosomes. Associations among lncRNA-miRNA-mRNA networks were validated by RNA pulldown and RNA immunoprecipitation and dual luciferase assays. Increased M1 polarization but decreased M2 polarization of retinal microglia was observed in DR mice. HG-treated M\u00fcller cell\u2013derived exosomes transported OGRU into microglia and promoted microglia polarization toward the M1 phenotype. Mechanistically, OGRU served as a competing endogenous RNA for miR-320-3p, miR-221-3p, and miR-574-5p to regulate aldose reductase (AR), PFKFB3, and glucose transporter 1 (GLUT1) expression in microglia, respectively. Loss of miR-320-3p\/miR-221-3p\/miR-574-5p or reinforced AR\/PFKFB3\/GLUT1 abrogated OGRU silencing\u2013mediated microglia polarization in\u00a0vitro. In vivo studies further showed that OGRU\/miR-320-3p\/AR, OGRU\/miR-221-3p\/PFKFB3, and OGRU\/miR-574-5p\/GLUT1 axes regulated microglia polarization in DR mice. Collectively, M\u00fcller cell\u2013derived exosomal OGRU regulated microglia polarization in DR by modulating OGRU\/miR-320-3p\/AR, OGRU\/miR-221-3p\/PFKFB3, and OGRU\/miR-574-5p\/GLUT1 axes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db23-1015","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:26:12Z","timestamp":1724415972000},"page":"1919-1934","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":16,"title":["M\u00fcller Cells Harboring Exosomal lncRNA OGRU Modulate Microglia Polarization in Diabetic Retinopathy by Serving as miRNA 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JiPing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YaoYun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"QianQian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Second Affiliated Hospital, 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