{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:38:19Z","timestamp":1790703499314,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY26970, P30EY021725, P30GM122744"],"award-info":[{"award-number":["R01EY26970, P30EY021725, P30GM122744"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in M\u00fcller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viability under diabetic conditions. Mouse primary MCs and cells of a rat MC line, rMC1, were used in investigating MC viability and BDNF production under diabetic conditions. VEGF-stimulated BDNF production was confirmed in mice. The mechanism of BDNF-mediated MC viability was examined using siRNA knockdown. Under diabetic conditions, recombinant VEGF (rVEGF) stimulated MC viability and BDNF production in a dose-dependent manner. rBDNF also supported MC viability in a dose-dependent manner. Targeting BDNF receptor tropomyosin receptor kinase B (TRK-B) with siRNA knockdown substantially downregulated the activated (phosphorylated) form of serine\/threonine-specific protein kinase (AKT) and extracellular signal-regulated kinase (ERK), classical survival and proliferation mediators. Finally, the loss of MC viability in TrkB siRNA transfected cells under diabetic conditions was rescued by rBDNF. Our results provide direct evidence that VEGF is a positive regulator for BDNF production in diabetes for the first time. This information is essential for developing BDNF-mediated neuroprotection in DR and hypoxic retinal diseases, and for improving anti-VEGF treatment for these blood\u2013retina barrier disorders, in which VEGF is a major therapeutic target for vascular abnormalities.<\/jats:p>","DOI":"10.3390\/biom11050712","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T02:14:05Z","timestamp":1620699245000},"page":"712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["VEGF Mediates Retinal M\u00fcller Cell Viability and Neuroprotection through BDNF in Diabetes"],"prefix":"10.3390","volume":"11","author":[{"given":"Yun-Zheng","family":"Le","sequence":"first","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Xu","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Eye Center of Xiangya Hospital, Central South University and Hunan Key Laboratory of Ophthalmology, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-1876","authenticated-orcid":false,"given":"Ana J.","family":"Chucair-Elliott","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"College of Biological Engineering, Henan University of Technology, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meili","family":"Zhu","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.visres.2017.03.013","article-title":"Muller cells and diabetic retinopathy","volume":"139","author":"Coughlin","year":"2017","journal-title":"Vis. 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