Hypoxia-inducible factor-1α: A promising therapeutic target for vasculopathy in diabetic retinopathy

Pharmacol Res. 2020 Sep:159:104924. doi: 10.1016/j.phrs.2020.104924. Epub 2020 May 25.

Abstract

Diabetic retinopathy (DR) is a serious condition that can cause blindness in diabetic patients. It is a neurovascular disease, but the pathogenesis leading to the onset of this disease is still not completely understood. However, hypoxia with subsequent neovascularization is a characteristic phenomenon observed with DR. Cellular response to hypoxia is mediated by the transcriptional regulator hypoxia-inducible factor (HIF). Long-term research has shown that one isotype of HIF, HIF-1α, may play a pivotal role under hypoxic conditions, and an increasing number of studies have shown that HIF-1α and its target genes contribute to retinal neovascularization. Therefore, targeting HIF-1α may lead to more effective DR treatments. This review describes the possible mechanisms of HIF-1α in neovascularization of DR. Furthermore, various inhibitors of HIF-1α that may have viable potential in the treatment of DR are also discussed.

Keywords: Diabetic retinopathy; Hypoxia-inducible factor-1α; Inhibitor; Neovascularization; Vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / genetics
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Gene Expression Regulation
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Neovascularization, Pathologic*
  • Protein Conformation
  • Signal Transduction
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A