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Abnormal vessel formation is the pathological hallmark of neovascular ROP. In forming vessels, vascular endothelial growth factor (VEGF) is an important stimulator. The current anti-ROP therapy has focused on bevacizumab, a monoclonal antibody against VEGF, and pazopanib, a tyrosine kinase inhibitor on the VEGF receptor (VEGFR). Several lines of evidence have proposed that natural compounds may be more effective and safer for anti-VEGF function. Resveratrol, a common natural compound, binds to VEGF and blocks its interaction with VEGFR, thereafter suppressing angiogenesis. Here, we evaluate the efficacy of intravitreal injection, or topical instillation (eye drops), of resveratrol into the eyes of mice suffering from oxygen-induced retinopathy, i.e., developing ROP. The treatment of resveratrol significantly relieved the degree of vascular distortion, permeability and hyperplasia; the efficacy could be revealed by both methods of resveratrol application. In parallel, the treatments of resveratrol inhibited the retinal expressions of VEGF, VEGFR and CD31. Moreover, the applied resveratrol significantly relieved the damage caused by oxygen radicals through upregulating the level of superoxide dismutase (SOD) and downregulating the level of malondialdehyde (MDA) in the retina. Taken together, the potential therapeutic benefit of resveratrol in pro-angiogenic diseases, including retinopathy, can be considered.<\/jats:p>","DOI":"10.3390\/ijms23126455","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T02:25:33Z","timestamp":1654827933000},"page":"6455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Resveratrol, an Inhibitor Binding to VEGF, Restores the Pathology of Abnormal Angiogenesis in Retinopathy of Prematurity (ROP) in Mice: Application by Intravitreal and Topical Instillation"],"prefix":"10.3390","volume":"23","author":[{"given":"Wei-Hui","family":"Hu","sequence":"first","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6137-3877","authenticated-orcid":false,"given":"Ka-Wing","family":"Leung","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518063, China"},{"name":"Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Duan","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518063, China"},{"name":"Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Xia (Tina)","family":"Dong","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"},{"name":"Shenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518063, China"},{"name":"Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1188-9023","authenticated-orcid":false,"given":"Qi-Wei","family":"Qin","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl Wah-Keung","family":"Tsim","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"},{"name":"Shenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen 518063, China"},{"name":"Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nature04483","article-title":"Angiogenesis as a therapeutic target","volume":"438","author":"Ferrara","year":"2005","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0092-8674(00)80108-7","article-title":"Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis","volume":"86","author":"Hanahan","year":"1996","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1056\/NEJMe058142","article-title":"Angiogenic pathways in diabetic retinopathy","volume":"353","author":"Aiello","year":"2005","journal-title":"N. 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