Resveratrol prevents the development of choroidal neovascularization by modulating AMP-activated protein kinase in macrophages and other cell types

Norihiro Nagai, Shunsuke Kubota, Kazuo Tsubota, Yoko Ozawa

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The development of choroidal neovascularization (CNV) is a critical step in the pathogenesis of age-related macular degeneration (AMD), a vision-threatening disease. In this study, we used a mouse model of AMD to study the protective effects of resveratrol (RSV) supplementation against CNV as well as the underlying molecular mechanisms. Mice were orally pretreated with RSV daily for 5. days. On the fifth day, the mice underwent laser photocoagulation to induce CNV. One week after laser treatment, CNV volume was significantly lower in the RSV-treated mice compared with vehicle-treated animals. In addition, RSV treatment significantly inhibited macrophage infiltration into the retinal pigment epithelium (RPE)-choroid and suppressed the expression of inflammatory and angiogenic molecules, including vascular endothelial growth factor, monocyte chemotactic protein-1 and intercellular adhesion molecule-1. Importantly, RSV prevented the CNV-induced decrease in activated AMP-activated protein kinase and increase in activated nuclear factor-κB in the RPE-choroid complex. The regulatory effects of RSV on these molecules were confirmed in RPE, microvascular endothelial and macrophage cell lines. Inhibition of macrophage infiltration by RSV was confirmed by in vitro scratch and migration assays. RSV suppressed CNV development, reducing the levels of multiple cytokines secreted from several cell types and inhibiting macrophage migration. The direct effects of RSV on each cell type were confirmed in vitro. Although further studies are needed, RSV could potentially be applied in the clinic to prevent CNV development in AMD.

Original languageEnglish
Pages (from-to)1218-1225
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume25
Issue number11
DOIs
Publication statusPublished - 2014 Nov 1

Keywords

  • AMPK
  • Inflammation
  • Macrophage
  • Neovascularization
  • Resveratrol
  • Retina

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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