Inhibition of choroidal neovascularization by homoisoflavanone, a new angiogenesis inhibitor

Mol Vis. 2008 Mar 18:14:556-61.

Abstract

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in elderly. The detailed mechanism of choroidal neovascularization (CNV) leads to severe vision loss in patients with AMD. This study was undertaken to evaluate the inhibitory effect of homoisoflavanone on CNV.

Methods: Antiangiogenic activity of homoisoflavanone was evaluated by in vitro tube formation assay of human umbilical vein endothelial cells (HUVECs) and cell migration assay of HUVECs., Homoisoflavanone or PBS was injected intravitreously into a mouse model of laser-photocoagulation-induced CNV. Fluorescein angiography and vessel counting in cross sections were employed to examine CNV lesions. The toxicity of homoisoflavanone was evaluated through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) assay in HUVECs as well as histological examination and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining in the retina.

Results: Homoisoflavanone effectively inhibited in vitro tube formation and cell migration of HUVECs. Interestingly, homoisoflavanone significantly reduced CNV and its leakage in a mouse model of laser-photocoagulation-induced CNV. In addition, homoisoflavanone showed no effect on cell viability of HUVECs and no retinal toxicity in a concentration range of 1-10 microM.

Conclusions: Our data suggest that homoisoflavanone is a potent inhibitor of CNV and may be applied in the treatment of other vasoproliferative retinopathies and tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Capillary Permeability / drug effects
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / metabolism
  • Choroidal Neovascularization / pathology
  • Choroidal Neovascularization / prevention & control*
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Female
  • Humans
  • Isoflavones / administration & dosage
  • Isoflavones / pharmacology*
  • Laser Coagulation
  • Mice
  • Mice, Inbred C57BL
  • Retina / drug effects

Substances

  • 5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one
  • Angiogenesis Inhibitors
  • Isoflavones