Inhibition of corneal neovascularization by a peroxisome proliferator-activated receptor-gamma ligand.
OBJECTIVE
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.
Sarayba
Melvin A
MA
Department of Ophthalmology, University of California, 118 Med Surge I, Irvine, CA 92697-4375, USA.
Li
Li
L
Tungsiripat
Tulaya
T
Liu
Norman H
NH
Sweet
Paula M
PM
Patel
Anup J
AJ
Osann
Kathryn E
KE
Chittiboyina
Amar
A
Benson
Stephen C
SC
Pershadsingh
Harrihar A
HA
Chuck
Roy S
RS
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D003315:Cornea / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D016510:Corneal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008858:Microscopy, Phase-Contrast / Q000379:methods; D047495:PPAR gamma / Q000032:analysis / Q000494:pharmacology*; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D000077205:Pioglitazone