Negative regulators of angiogenesis: important targets for treatment of exudative AMD

Clin Sci (Lond). 2017 Jul 5;131(15):1763-1780. doi: 10.1042/CS20170066. Print 2017 Aug 1.

Abstract

Angiogenesis contributes to the pathogenesis of many diseases including exudative age-related macular degeneration (AMD). It is normally kept in check by a tightly balanced production of pro- and anti-angiogenic factors. The up-regulation of the pro-angiogenic factor, vascular endothelial growth factor (VEGF), is intimately linked to the pathogenesis of exudative AMD, and its antagonism has been effectively targeted for treatment. However, very little is known about potential changes in expression of anti-angiogenic factors and the role they play in choroidal vascular homeostasis and neovascularization associated with AMD. Here, we will discuss the important role of thrombospondins and pigment epithelium-derived factor, two major endogenous inhibitors of angiogenesis, in retinal and choroidal vascular homeostasis and their potential alterations during AMD and choroidal neovascularization (CNV). We will review the cell autonomous function of these proteins in retinal and choroidal vascular cells. We will also discuss the potential targeting of these molecules and use of their mimetic peptides for therapeutic development for exudative AMD.

Keywords: PEDF; angiogenesis; endothelial cells; pericytes; retinal pigment epithelial cells; thrombospondins.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / physiology*
  • Angiogenesis Inhibitors / therapeutic use
  • Angiostatins / therapeutic use
  • Choroidal Neovascularization / drug therapy
  • Choroidal Neovascularization / physiopathology*
  • Endostatins / therapeutic use
  • Eye Proteins / physiology*
  • Humans
  • Macular Degeneration / drug therapy
  • Macular Degeneration / physiopathology*
  • Molecular Targeted Therapy / methods
  • Nerve Growth Factors / physiology*
  • Serpins / physiology*
  • Thrombospondins / physiology*

Substances

  • Angiogenesis Inhibitors
  • Endostatins
  • Eye Proteins
  • Nerve Growth Factors
  • Serpins
  • Thrombospondins
  • pigment epithelium-derived factor
  • Angiostatins