{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:44:34Z","timestamp":1792601074918,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic retinopathy (DR) is a major complication of diabetes mellitus, characterised by retinal vasculopathy and oxidative stress. Semaglutide, a glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101RA), has demonstrated cardiovascular benefits but has also been associated with mixed effects on DR progression. This study investigates the potential of semaglutide to attenuate DR progression by ameliorating retinal vasculopathy and oxidative stress in both in vivo and in vitro models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo, a streptozotocin\u2010induced DR rat model was used, and semaglutide (100\u2009\u03bcg\/kg\/week) was administered for 5\u2009weeks. The retinal pathological symptoms, vascular lesions, neuronal apoptosis, and inflammation were evaluated by HE staining, PAS staining, immunohistochemistry staining, and ELISA assay. In vitro, human retinal microvascular endothelial cells (HRMECs) exposed to a high glucose (HG) environment were treated with semaglutide (5\u2009nM) to assess oxidative stress, vascular endothelial conditions, and inflammation by immunofluorescence and ELISA assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Semaglutide significantly reduced the blood glucose levels of DR rats and improved their retinal function. It increased the thickness of the inner nuclear layer of the retina and alleviated neuronal apoptosis. Semaglutide also alleviated retinal vascular lesions and inflammatory responses, which were demonstrated by the increase in retinal vascular tight junction markers and the reduction in pro\u2010inflammatory cytokines. In high glucose\u2010treated HRMECs, semaglutide inhibited oxidative stress and cellular inflammation, and simultaneously downregulated the expression of VFGFA. In the semaglutide\u2010treated group, the expression of ZO\u20101 was restored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Semaglutide slows the progression of diabetic retinopathy by improving retinal vascular lesions and reducing oxidative stress. Its mechanism of action may involve the reduction of inflammation and apoptosis. Its overall protective effect on retinal function and oxidative stress highlights its potential as a therapeutic drug for diabetic retinopathy. Further mechanisms and clinical studies are needed to validate these findings and assess the long\u2010term effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70107","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:15:04Z","timestamp":1757564104000},"page":"7085-7096","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Semaglutide attenuates diabetic retinopathy progression via ameliorating retinal vasculopathy and oxidative stress in vivo and in vitro"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7572-0420","authenticated-orcid":false,"given":"Xiao","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pharmacy Beijing Tongren Hospital, Capital Medical University  Beijing 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