Vascular endothelial growth factor and diabetic retinopathy: Role of oxidative stress

Ruth B Caldwell, Manuela Bartoli, M. Ali Behzadian, Azza E.B. El-Remessy, Mohamed Al-Shabrawey, Daniel H. Platt, Gregory I Liou, Robert William Caldwell

Research output: Contribution to journalReview article

172 Scopus citations

Abstract

Retinal neovascularization and macular edema are central features of diabetic retinopathy, a major cause of blindness in working age adults. The currently established treatment for diabetic retinopathy targets the vascular pathology by laser photocoagulation. This approach is associated with significant adverse effects due the destruction of neural tissue and is not always effective. Characterization of the molecular and cellular processes involved in vascular growth and hyperpermeability has led to the recognition that the angiogenic growth factor and vascular permeability factor VEGF (vascular endothelial growth factor) play a pivotal role in the retinal microvascular complications of diabetes. Thus, VEGF represents an important target for therapeutic intervention in diabetic retinopathy. Agents that directly inhibit the actions of VEGF and its receptors show considerable promise, but have not proven to be completely effective in blocking pathological angiogenesis. Therefore, a better understanding of the molecular events that control VEGF expression and mediate its downstream actions is important to define more precise therapeutic targets for intervention in diabetic retinopathy. This review highlights the current understanding of the process by which VEGF gene expression is regulated and how VEGF's biological effects are altered during diabetes. In particular, cellular and molecular alterations seen in diabetic models are considered in the context of high glucose-mediated oxidative stress effects on VEGF expression and action. Potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological actions in the diabetic retina are considered.

Original languageEnglish (US)
Pages (from-to)511-524
Number of pages14
JournalCurrent Drug Targets
Volume6
Issue number4
DOIs
Publication statusPublished - Jun 1 2005

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Keywords

  • Diabetes
  • Diabetic retinopathy
  • Drug therapy
  • High glucose
  • Hyperglycemia
  • Oxidative stress
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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