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

Int J Mol Sci. 2022 Jun 9;23(12):6455. doi: 10.3390/ijms23126455.

Abstract

Retinopathy of prematurity (ROP) is a severe eye disease leading to blindness. 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.

Keywords: age-related macular degeneration; anti-VEGF; natural product; resveratrol; retinopathy of prematurity.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Bevacizumab / therapeutic use
  • Mice
  • Neovascularization, Pathologic / drug therapy
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use
  • Retinopathy of Prematurity* / drug therapy
  • Retinopathy of Prematurity* / pathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Bevacizumab
  • Resveratrol

Grants and funding

This work is supported by Hong Kong Innovation Technology Fund (UIM/385, ITS/500/18FP; ITCPD/17-9); Shenzhen Science and Technology Innovation Committee (ZDSYS201707281432317); Guangzhou Science and Technology Committee Research Grant (GZSTI16SC02 & GZSTI17SC02); The Key-Area Research and Development Program of Guangdong Province (2020B1111110006); Special project of Foshan University of science and technology in 2019 (FSUST19-SRI10); GBA Institute of Collaborate Innovation (GICI-022); Zhongshan Municipal Bureau of Science and Technology (2019AG035); Hong Kong RGC-GFC 16100921; Hong Kong RGC Theme-based Research Scheme (T13-605/18-W); TUYF19SC02, PD18SC01 and HMRF18SC06; HMRF20SC07; AFD20SC01; and Guangdong Basic and Applied Basic Research Foundation (2020A1515110187).