{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T17:15:44Z","timestamp":1781370944316,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"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, R01EY20900, P30EY021725, P30GM122744"],"award-info":[{"award-number":["R01EY26970, R01EY20900, P30EY021725, P30GM122744"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81070738; 81300775"],"award-info":[{"award-number":["81070738; 81300775"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008569","name":"Oklahoma Center for the Advancement of Science and Technology","doi-asserted-by":"publisher","award":["HR20-065"],"award-info":[{"award-number":["HR20-065"]}],"id":[{"id":"10.13039\/100008569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Vascular endothelial growth factor (VEGF) is a major therapeutic target for blood\u2013retina barrier (BRB) breakdown in diabetic retinopathy (DR), age-related macular degeneration (AMD), and other hypoxic retinal vascular disorders. To determine whether VEGF is a direct regulator of retinal neuronal function and its potential role in altering vision during the progression of DR, we examined the immediate impact of recombinant VEGF (rVEGF) on photoreceptor function with electroretinography in C57BL6 background wild-type (WT) and Akita spontaneous diabetic mice. Shortly after intravitreal injections, rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner in dark-adapted 1.5-mo-old WT mice. Compared with WT controls, 5-mo-old Akita spontaneous diabetic mice demonstrated a significant reduction in scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes. However, the effect of rVEGF altered photoreceptor function in WT controls was diminished in 5-mo-old Akita spontaneous diabetic mice. In conclusion, our results suggest that VEGF is a direct functional regulator of photoreceptors and VEGF up-regulation in DR is a contributing factor to diabetes-induced alteration of photoreceptor function. This information is critical to the understanding of the therapeutic effect and to the care of anti-VEGF drug-treated patients for BRB breakdown in DR, AMD, and other hypoxic retinal vascular disorders.<\/jats:p>","DOI":"10.3390\/biom11070988","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T22:02:04Z","timestamp":1625522524000},"page":"988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function"],"prefix":"10.3390","volume":"11","author":[{"given":"Jianyan","family":"Hu","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 Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai 200233, 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"}]},{"given":"Dai","family":"Li","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":"School of Optometry, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai 200233, China"},{"name":"Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Zheng","family":"Le","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":"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"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1167\/iovs.04-0247","article-title":"Death of retinal neurons in streptozotocin-induced diabetic mice","volume":"45","author":"Martin","year":"2004","journal-title":"Investig. 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