Lipid hydroperoxide induced corneal neovascularization in hyperglycemic rabbits.
OBJECTIVE
To compare the effect of hyperglycemia on corneal neovascularization (NV) induced by linoleic acid hydroperoxide (LHP) in a rabbit model.


METHODS
Male New Zealand rabbits received 80 mg/kg alloxan i.v. and subsequently developed hyperglycemia. Four weeks later, 10 microl of LHP (40 mM) was injected into corneal stroma 5 mm from the superior limbus with a 30 gauge needle. Vessel growth area from the limbal vasculature was measured over a period of 2 weeks and was correlated with plasma levels of insulin, HbA(1c), and corneal vascular endothelial growth factor (VEGF).


RESULTS
Two days after alloxan, blood glucose was increased from 97 +/- 4 mg/dl in the untreated control group to 413 +/- 3 mg/dl. At 24 and 72 hours after LHP injection, VEGF in cornea of hyperglycemic rabbits was elevated 2 to 4 times above that of normoglycemic rabbits. At 14 days after LHP injection, the normoglycemic rabbits vessel growth area measured 2.42 +/- 0.31 mm(2), but in the hyperglycemic group, vessel growth area was significantly increased to 7.96 +/- 2.26 mm(2) (p < 0.05). At the end of the experimental period, HbA(1c) was elevated from 3.9 +/- 0.8 % to 8.4 +/- 0.6 % and insulin was decreased from 440 +/- 123.9 pg/ml to 24 +/- 11.0 pg/ml.


CONCLUSIONS
These data suggest that hyperglycemia may sensitize corneal and vascular endothelial cells, perhaps by glucose derived radicals, which enhance production of additional LHP through endogenous propagation reactions, and raise in turn the concentration of VEGF levels to induce an enhanced, sustained NV response.
Higa
Akira
A
Department of Ophthalmology, Showa University School of Medicine, Tokyo, Japan.
Nakanishi-Ueda
Takako
T
Arai
Yuichiro
Y
Tsuchiya
Tadaharu
T
Ueda
Toshihiko
T
Fukuda
Shohei
S
Watanabe
Kaori
K
Kan
Kazuaki
K
Yasuhara
Hajime
H
Koide
Ryohei
R
Armstrong
Donald
D
D000496:Alloxan / Q000633:toxicity; D000818:Animals; D001786:Blood Glucose; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008041:Linoleic Acids / Q000633:toxicity*; D008054:Lipid Peroxides / Q000633:toxicity*; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000496:Alloxan; D001786:Blood Glucose; D016228:Endothelial Growth Factors; D006442:Glycated Hemoglobin; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C008285:linoleic acid hydroperoxide