{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:17:07Z","timestamp":1793305027086,"version":"4.5.0"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["FOR2240"],"award-info":[{"award-number":["FOR2240"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["SFB\/CRC1607"],"award-info":[{"award-number":["SFB\/CRC1607"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Center of Molecular Medicine","award":["2635\/8322\/01"],"award-info":[{"award-number":["2635\/8322\/01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,8]]},"abstract":"<jats:p>The loss of integrity of the blood retina barrier (BRB) is a key pathological hallmark of vision-threatening complications in diabetic retinopathy (DR). Although DR is considered a microvascular disease, mounting evidence from mouse models and patients show that inflammation is closely connected with microvasculopathy. Inflammatory responses during retinal pathophysiology are often orchestrated by microglia, resident innate immune cells of the retina. However, the precise role of microglia activity during DR pathogenesis remains elusive. Here, we used an anti-PDGFR\u03b2 antibody and inducible endothelial cell\u2013specific PDGFB-KO during postnatal development of retinal vasculature to reproduce a key feature of DR pathology in mice. In addition, we applied a minocycline therapy to modulate retinal inflammation. Postnatal depletion of pericytes or loss of PDGFB in retinal vessels altered BRB integrity and triggered secretion of angiogenic and inflammatory factors with concomitant microglia reactivity, which was sustained in retinas of adult mice. Microglia reactivity was accompanied by upregulation of disease-associated genes. Notably, minocycline attenuated the cycle of inflammatory responses in young and mature retinas, thereby preserving retinal vascular and structural integrity in mice. Together, our findings suggest that immunomodulation of microglia-driven inflammatory responses preserves retinal vasculature and maintains BRB integrity in 2 different mouse models of human DR.<\/jats:p>","DOI":"10.1172\/jci.insight.184465","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T12:00:22Z","timestamp":1751371222000},"source":"Crossref","is-referenced-by-count":11,"title":["Immunomodulation of inflammatory responses preserves retinal integrity in murine models of pericyte-depletion retinopathy"],"prefix":"10.1172","volume":"10","author":[{"given":"Urbanus Muthai","family":"Kinuthia","sequence":"first","affiliation":[{"name":"Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany."},{"name":"Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Moehle","sequence":"additional","affiliation":[{"name":"Center of Excellence for Fluorescent Bioanalytics, University of Regensburg, Regensburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3031-7677","authenticated-orcid":true,"given":"Ralf H.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine and University of M\u00fcnster, Faculty of Medicine, M\u00fcnster, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Langmann","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany."},{"name":"Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2017.05.009"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020412"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16330"},{"issue":"5","key":"B4","first-page":"1217","article-title":"Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis","volume":"41","author":"Hughes","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.11.001"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.01.023"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93751"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.07.032"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S128509"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2017.6565"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02802-4"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2007.65"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.11.3.16"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1160"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10876"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/4920937"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2308214120"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.90905"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15296"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12139"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.108953"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0431-4"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.206633"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0239108"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.5.1559"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5176"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58039-x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.564077"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2023290118"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1101\/gad.266803"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf418"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.025"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135296"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2020.107641"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.2.26"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02589-6"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16400-8"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-24621"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10123222"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-017-0913-0"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-023-03155-1"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02931-y"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1186\/s40942-023-00453-0"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215621"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1345382"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.11.009"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160442"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01122.x"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276311"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-149"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-022-02150-9"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.06.025"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2022.01.021"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72179-0"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-174508"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027385"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/184465\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T15:12:57Z","timestamp":1779030777000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/184465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":58,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8,8]]},"published-print":{"date-parts":[[2025,8,8]]}},"alternative-id":["10.1172\/jci.insight.184465"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.184465","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"article-number":"e184465"}}