Retinal diseases regulated by hypoxia—basic and clinical perspectives: A comprehensive review

Ari Shinojima, Deokho Lee, Kazuo Tsubota, Kazuno Negishi, Toshihide Kurihara

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


In recent years, the number of patients with age-related macular degeneration (AMD) is increasing worldwide along with increased life expectancy. Currently, the standard treatment for wet-AMD is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. The upstream of VEGF is hypoxia-inducible factor (HIF), a master regulator of hypoxia-responsive genes responsive to acute and chronic hypoxia. HIF activation induces various pathological pro-angiogenic gene expressions including VEGF under retinal hypoxia, ultimately leading to the development of ocular ischemic neovascular diseases. In this regard, HIF is considered as a promising therapeutic target in ocular ischemic diseases. In clinical ophthalmology, abnormal hypofluorescent areas have been detected in the late-phase of indocyanine green angiography, which are thought to be lipid deposits at the level of Bruch’s membrane to choriocapillaris in vitreoretinal diseases. These deposits may interfere with the oxygen and nutrients that should be supplied to the retinal pigment epithelium, and that HIF/VEGF is highly suspected to be expressed in the hypoxic retinal pigment epithelium, leading to neovascularization. In this review, we comprehensively summarize pathophysiology of AMD-related ocular diseases with the HIF/VEGF pathway from basic and clinic researches with recent findings.

Original languageEnglish
Article number5496
JournalJournal of Clinical Medicine
Issue number23
Publication statusPublished - 2021 Dec 1


  • Age-related macular degeneration
  • Angiography
  • Auto-fluorescence
  • Central serous chorioretinopathy
  • Choroidal neovascularization
  • Hypofluorescent
  • Hypoxia-inducible factor
  • Indocyanine green
  • Optical coherence tomography
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • General Medicine


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