The inhibition of retinal neovascularization by gold nanoparticles via suppression of VEGFR-2 activation

Biomaterials. 2011 Mar;32(7):1865-71. doi: 10.1016/j.biomaterials.2010.11.030. Epub 2010 Dec 9.

Abstract

The pathological angiogenesis in the retina is the major cause of vision loss at all ages. In particular, retinopathy of prematurity (ROP) is a leading cause of blindness in children. This study investigated whether gold nanoparticle (GNP) could inhibit retinal neovascularization in the animal model of ROP. Intravitreal injection of GNP significantly inhibited retinal neovascularization in the mouse model of ROP. In addition, GNP effectively suppressed VEGF-induced in vitro angiogenesis of retinal microvascular endothelial cells including proliferation, migration and capillary-like networks formation. GNP blocked VEGF-induced auto-phosphorylation of VEGFR-2 to inhibit consequently ERK 1/2 activation. GNP never affected on the cellular viability of retinal microvascular endothelial cells and induced no retinal toxicity. Our data suggest that GNP could be a potent inhibitor to retinal neovascularization without retinal toxicity. Furthermore, GNP could be extensively applied to variable vaso-proliferative retinopathies mediated by VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Gold / chemistry*
  • Humans
  • Infant, Newborn
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Phosphorylation / drug effects
  • Retinopathy of Prematurity / drug therapy
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Gold
  • Vascular Endothelial Growth Factor Receptor-2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3