Effect of a dihydrobenzofuran derivative on lipid hydroperoxide-induced rabbit corneal neovascularization.

Abstract

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.

• Authors: Hirotsugu Ogura, Takako Nakanishi-Ueda, Toshihiko Ueda, Shinichi Iwai, Seiichi Uchida, Yuta Saito, Yoko Taguchi, Hajime Yasuhara, Donald Armstrong, Katsuji Oguchi, Ryohei Koide
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 103 Issue 2 Pg. 234-40 (Feb 2007) ISSN: 1347-8613 [Print] Japan
• PMID: 17287586 (Publication Type: Journal Article)

Chemical References

• A-3922
• Angiogenesis Inhibitors
• Benzofurans
• Lipid Peroxides
• Vascular Endothelial Growth Factor A
• Matrix Metalloproteinase 9

Topics

• Angiogenesis Inhibitors (administration & dosage, pharmacokinetics, therapeutic use)
• Animals
• Benzofurans (pharmacology)
• Chromatography, High Pressure Liquid
• Corneal Neovascularization (pathology, prevention & control)
• Extracellular Matrix (enzymology, pathology)
• Image Processing, Computer-Assisted
• Injections, Intraperitoneal
• Lipid Peroxides (pharmacology)
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Rabbits
• Retinal Vessels (pathology)
• Vascular Endothelial Growth Factor A (pharmacology)