Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization

Exp Eye Res. 1997 Jun;64(6):971-8. doi: 10.1006/exer.1997.0292.


Thalidomide, when administered orally, is an inhibitor of angiogenesis in the basic fibroblast growth factor (bFGF)-induced rabbit cornea micropocket assay. We now show in the mouse that thalidomide given intraperitoneally but not orally significantly inhibits bFGF-induced and vascular endothelial growth factor (VEGF)-induced corneal neovascularization. We further demonstrate that this inhibition is independent from thalidomide's ability to suppress tumor necrosis factor-alpha (TNF-alpha) production. Experiments examining thalidomide's enantiomers reveal-that the S(-)-enantiomer has the strongest antiangiogenic activity in VEGF-induced and bFGF-induced corneal neovascularization. Structure activity studies suggest that thalidomide's anti-angiogenic activity is related to the open ring metabolites resulting from hydrolysis. Together these data support a correlation between thalidomide's antiangiogenic and teratogenic activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cornea / blood supply*
  • Corneal Neovascularization / etiology
  • Corneal Neovascularization / prevention & control*
  • Endothelial Growth Factors
  • Female
  • Fibroblast Growth Factor 2
  • Glutamates / therapeutic use
  • Injections, Intraperitoneal
  • Lymphokines
  • Mice
  • Mice, Inbred C57BL
  • Structure-Activity Relationship
  • Teratogens / chemistry
  • Teratogens / pharmacology*
  • Thalidomide / analogs & derivatives
  • Thalidomide / chemistry
  • Thalidomide / pharmacology*
  • Thalidomide / therapeutic use
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Glutamates
  • Lymphokines
  • N-phthalimidino glutaric acid
  • Teratogens
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
  • 2-(2,6-dioxopiperidin-3-yl)phthalimidine
  • N-phthaloylglutamic acid
  • Thalidomide