{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:27:39Z","timestamp":1793878059372,"version":"4.7.0"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Therapeutic strategies in the management of diabetic retinal diseases have typically employed anti\u2013vascular endothelial growth factor A (anti\u2013VEGF-A) therapies. While generally effective, clinical trials and real-world analyses demonstrate that a substantial proportion of patients do not show adequate response to this drug class, with retinal edema persisting in upwards of 60% of cases after one to two years of therapy, exhibiting suboptimal visual outcomes and insufficient disease control, with VEGF independent pathways remaining unaddressed. Inflammation is increasingly recognized as a pivotal pathogenic driver in diabetic eye disease, with Interleukin-6 (IL-6) identified as a central mediator of acute and chronic inflammatory responses. This review discusses the role of inflammation in diabetic retinal disease and synthesizes emerging evidence regarding the therapeutic targeting of IL-6. We highlight the differences between cis-, trans-, and cluster signaling, and describe the IL-6 buffer system. We review preclinical evidence demonstrating how IL-6 signaling disrupts the blood-retinal barrier, both directly and synergistically with VEGF. Finally, we describe the emerging clinical evidence for selective IL-6 and bispecific IL-6\/VEGF monoclonal antibodies currently in drug development. These novel approaches aim to address the multiple pathogenic pathways that drive Diabetic Macular Edema (DME), with potential to show superior efficacy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1805665","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:15:29Z","timestamp":1776399329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The role of interleukin-6 in diabetic retinal disease: pathophysiology and therapeutic targeting"],"prefix":"10.3389","volume":"17","author":[{"given":"Rachael E. A.","family":"Harlow","sequence":"first","affiliation":[{"name":"Roche Pharma Research and Early Development, F. 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