Inhibition of corneal neovascularization by a peroxisome proliferator-activated receptor-gamma ligand

Exp Eye Res. 2005 Mar;80(3):435-42. doi: 10.1016/j.exer.2004.10.009.


Purpose: To determine the efficacy of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in inhibiting corneal neovascularization.

Methods: Twenty-six adult male Sprague-Dawley rats were randomly divided into three groups. Each group received intrastromal polymer micropellets containing one of the following: Group 1, no active ingredient (n=10); Group 2, vascular endothelial growth factor (VEGF) (n=7); Group 3, VEGF and pioglitazone (n=9). Neovascularization was evaluated 7 days after pellet implantation. After systemic India ink injection, digital photographs of the eyes were taken. The area and density of neovascularization were measured using imaging software.

Results: Mean area of neovascularization was 0.43+/-0.18 mm2 for Group 1, 2.87+/-0.48 mm2 for Group 2 and 2.10+/-0.22 mm2 for Group 3. Statistical analysis showed significant differences between Groups 1 and 2 and Groups 1 and 3. There was no significant difference between Groups 2 and 3. Mean density of neovascularization was 2.16+/-0.66 for Group 1, 27.14+/-2.93 for Group 2 and 12.02+/-2.24 for Group 3. All comparisons between groups were statistically significant (P<0.01).

Conclusions: Pioglitazone is effective in decreasing the density of angiogenesis in a VEGF-induced neovascular rat cornea model. There is possibility of even greater effect with higher doses of the drug. Pioglitazone is a promising drug for the treatment of ocular neovascularization.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western / methods
  • Cornea / chemistry
  • Cornea / drug effects
  • Cornea / pathology
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / prevention & control*
  • Hypoglycemic Agents / pharmacology*
  • Ligands
  • Male
  • Microscopy, Phase-Contrast / methods
  • PPAR gamma / analysis
  • PPAR gamma / pharmacology*
  • Pioglitazone
  • Rats
  • Rats, Sprague-Dawley
  • Thiazolidinediones / pharmacology*
  • Vascular Endothelial Growth Factor A / pharmacology


  • Hypoglycemic Agents
  • Ligands
  • PPAR gamma
  • Thiazolidinediones
  • Vascular Endothelial Growth Factor A
  • Pioglitazone