Citation:Zhang HM, Li XH, Chen M, Luo J. Intravitreal injection of resveratrol inhibits laser-induced murine choroidal neovascularization. Int J Ophthalmol 2020;13(6):886-892,doi:10.18240/ijo.2020.06.05
Intravitreal injection of resveratrol inhibits laser-induced murine choroidal neovascularization
Received:April 14, 2019  Revised:March 25, 2020
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DOI:10.18240/ijo.2020.06.05
Key Words:resveratrol  intravitreal injection  choroidal neovascularization  vascular endothelial growth factor receptor 2  tube formation  murine
Fund Project:Supported by the National Natural Science Foundation of China (No.81703134; No.81770952); Henan Province Nature Science Foundation of China (No.162300410296); Hunan Province Nature Science Foundation of China (No.2018JJ3772).
           
AuthorInstitution
Hui-Ming Zhang Department of Dermatology, the Second Xiangya Hospital, Central South University, Changsha , Hunan Province, China; Hunan Key Laboratory of Medical Epigenomics, Changsha , Hunan Province, China; Department of Pathology and Ophthalmology, Keck School of Medicine at University of Southern California, Los Angeles, California 90033, USA
Xiao-Hua Li Henan Provincial People’s Hospital
Mingjiazi Chen Henan Eye Hospital, Henan Eye Institute, Henan Key Laboratory of Ophthalmology and Vision Science
Jing Luo Henan Eye Hospital, Henan Eye Institute, Henan Key Laboratory of Ophthalmology and Vision Science
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Abstract:
      AIM: To determine the effects of intravitreal resveratrol (RSV) on murine laser-induced choroidal neovascularization (CNV).

    METHODS: The toxicity of RSV to choroidal endothelial cell (CEC) was measured using thiazolyl blue tetrazolium bromide (MTT) assay. Effects of RSV on choroidal endothelial cell (CEC) migration were evaluated with a modified Boyden chamber assay, while tube formation was evaluated in a 2-D gel assay. CNV was induced by laser photocoagulation in mice. The effects of intravitreal injection of RSV on CNV development were evaluated by fluorescein angiography (FA), confocal analysis of isolectin B4 labeled choroidal flat mounts, and histologic examination of CNV membranes. Immunostaining was used to analyze the expression and phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2).

    RESULTS: No significant cell toxicity was observed in CEC if the concentration of RSV was less than 200 μmol/L (P>0.05). RSV inhibited vascular endothelial growth factor (VEGF)-induced CEC migration (P<0.05) and tube formation (P<0.05) in vitro. Furthermore, intravitreal injection of RSV significantly inhibited laser induced CNV formation in mice. The FA leakage, CNV volume and CNV area analysis revealed that there were 41%, 45%, and 58% reduction in RSV-treated eyes (1.691±0.1032, 178 163±78 623 μm3 and 6508±619.0 μm2, respectively) compared with those in control (2.724±0.08447, 379 676±98 382 μm3 and 16 576±2646 μm2, respectively; P<0.05). Phospho-VEGFR2 expression was much weaker in the sections of CNV lesions in RSV injected mice compared with that in control (P<0.05).

    CONCLUSION: Intravitreal injection of RSV exerts an inhibitory effect on CNV, which may through suppressing endothelial cell migration, tube formation and VEGFR2 phosphorylation.

PMC FullText Html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270251/
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