Ocular Angiogenesis: Vascular Endothelial Growth Factor and Other Factors

Dev Ophthalmol. 2016:55:28-37. doi: 10.1159/000431129. Epub 2015 Oct 26.

Abstract

Systematic study of the mechanisms underlying pathological ocular neovascularization has yielded a wealth of knowledge about pro- and anti-angiogenic factors that modulate diseases such as neovascular age-related macular degeneration. The evidence implicating vascular endothelial growth factor (VEGF) in particular has led to the development of a number of approved anti-VEGF therapies. Additional proangiogenic targets that have emerged as potential mediators of ocular neovascularization include hypoxia-inducible factor-1, angiopoietin-2, platelet-derived growth factor-B and components of the alternative complement pathway. As for VEGF, knowledge of these factors has led to a product pipeline of many more novel agents that are in various stages of clinical development in the setting of ocular neovascularization. These agents are represented by a range of drug classes and, in addition to novel small- and large-molecule VEGF inhibitors, include gene therapies, small interfering RNA agents and tyrosine kinase inhibitors. In addition, combination therapy is beginning to emerge as a strategy to improve the efficacy of individual therapies. Thus, a variety of agents, whether administered alone or as adjunctive therapy with agents targeting VEGF, offer the promise of expanding the range of treatments for ocular neovascular diseases.

Publication types

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

MeSH terms

  • Angiopoietin-2 / physiology*
  • Complement Pathway, Alternative / physiology*
  • Eye / blood supply*
  • Humans
  • Hypoxia-Inducible Factor 1 / physiology*
  • Neovascularization, Pathologic / physiopathology*
  • Proto-Oncogene Proteins c-sis / physiology*
  • Vascular Endothelial Growth Factor A / physiology*

Substances

  • ANGPT2 protein, human
  • Angiopoietin-2
  • Hypoxia-Inducible Factor 1
  • Proto-Oncogene Proteins c-sis
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A