Rice bran and vitamin b6 suppress pathological neovascularization in a murine model of age‐related macular degeneration as novel hif inhibitors

Mari Ibuki, Deokho Lee, Ari Shinojima, Yukihiro Miwa, Kazuo Tsubota, Toshihide Kurihara

Research output: Contribution to journalArticlepeer-review

Abstract

Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age‐related macular degeneration (AMD) in the elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti‐VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti‐VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia‐inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE‐19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed VEGF mRNA induction under a CoCl2‐induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization.

Original languageEnglish
Article number8940
Pages (from-to)1-24
Number of pages24
JournalInternational journal of molecular sciences
Volume21
Issue number23
DOIs
Publication statusPublished - 2020 Dec 1

Keywords

  • Age‐related macular degeneration
  • Food ingredients
  • Hypoxia‐inducible factor
  • Retinal pigment epithelium
  • Rice bran
  • Vascular endothelial growth factor
  • Vitamin B6

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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