Effect of a dihydrobenzofuran derivative on lipid hydroperoxide-induced rabbit corneal neovascularization.
The aim of this study was to investigate the effect of A-3922, a dihydrobenzofuran derivative, on linoleic acid hydroperoxide (LHP)-induced corneal neovascularization (NV) in a rabbit model. Male New Zealand rabbits received intraperitoneal (i.p.) injections of 10 or 30 mg/kg per day A-3922 or its vehicle as control for 3 days. One day after i.p. injections, LHP was injected with a 30-gauge needle into the corneal stroma of the superior quadrant 4.5-mm below the limbus. Photographs of the vessels were taken for digital analysis with a surgical microscope. Vascular endothelial growth factor (VEGF) was measured using an immunoassay kit, and matrix metalloproteinase (MMP)-9 was measured by gelatin zymography in corneal samples. At 7 days post-LHP injection, the total vessel length was 26.7 +/- 3.8 mm in the control animals (n = 8), 16.1 +/- 0.8 mm in the A-3922 (10 mg/kg)-treated group (n = 5), and 11.4 +/- 2.1 mm in the 30 mg/kg group (n = 8, P<0.01 vs control), respectively. After LHP injection, the content of VEGF and MMP-9 activity were increased in the superior cornea, but these were not influenced by A-3922 treatments. These results indicate that LHP-induced corneal NV is inhibited by treatment with A-3922 and therefore may represent a potential pharmacological intervention for ocular neovascularization disorders.
Ogura
Hirotsugu
H
Department of Ophthalmology, School of Medicine, Showa University, Tokyo 142-8555, Japan.
Nakanishi-Ueda
Takako
T
Ueda
Toshihiko
T
Iwai
Shinichi
S
Uchida
Seiichi
S
Saito
Yuta
Y
Taguchi
Yoko
Y
Yasuhara
Hajime
H
Armstrong
Donald
D
Oguchi
Katsuji
K
Koide
Ryohei
R
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D016510:Corneal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D005109:Extracellular Matrix / Q000201:enzymology / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007274:Injections, Intraperitoneal; D008054:Lipid Peroxides / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011817:Rabbits; D012171:Retinal Vessels / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
C519314:A-3922; D020533:Angiogenesis Inhibitors; D001572:Benzofurans; D008054:Lipid Peroxides; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9