A Novel HIF Inhibitor Halofuginone Prevents Neurodegeneration in a Murine Model of Retinal Ischemia-Reperfusion

Hiromitsu Kunimi, Yukihiro Miwa, Hiroyoshi Inoue, Kazuo Tsubota, Toshihide Kurihara

Research output: Contribution to journalArticle

Abstract

Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume20
Issue number13
DOIs
Publication statusPublished - 2019 Jun 28

Fingerprint

ischemia
hypoxia
inhibitors
Reperfusion
Screening
Ischemia
Neuroprotective Agents
Derivatives
Hydrangea
Hypoxia-Inducible Factor 1
Retinal Diseases
intraocular pressure
Biological Products
Intraocular Pressure
homeostasis
Homeostasis
screening
halofuginone
Hypoxia
products

Keywords

  • halofuginone
  • HIF-1α
  • ischemia-reperfusion
  • neuroprotection

ASJC Scopus subject areas

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

Cite this

A Novel HIF Inhibitor Halofuginone Prevents Neurodegeneration in a Murine Model of Retinal Ischemia-Reperfusion. / Kunimi, Hiromitsu; Miwa, Yukihiro; Inoue, Hiroyoshi; Tsubota, Kazuo; Kurihara, Toshihide.

In: International journal of molecular sciences, Vol. 20, No. 13, 28.06.2019.

Research output: Contribution to journalArticle

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