The Effect of the Dihydrobenzofuran Derivative on Lipid Hydroperoxide–Induced Rabbit Corneal Neovascularization

Abstract

Abstract: : Purpose: To evaluate the effect of A–3922, dihydrobenzofuran derivative, on linoleic acid hydroperoxide(LHP)–induced corneal neovascularization in a rabbit model. Methods: Male New Zealand rabbits weighing 2.5–4 kg received 3 daily intraperitoneal injections of 10 and 30 mg/kg/day A–3922 dissolved in 1%NIKKOL HCO–60/DMSO=8/2, or buffer alone as control. One day after systemic equilibration, 10 µ L of LHP(40 mM) was injected with a 30 gauge needle into the corneal stroma of the superior quadrant 4.5 mm below the limbus. Maximum vessel length was measured by caliper and, photographs were taken for digital analysis with a surgical microscope at 1, 4, 7, 10, and 14 days after LHP injection. At sacrifice, vascular endothelial growth factor (VEGF) in the corneal tissue was measured by immunoassay kit(R &D system). Statistical analysis used multiple comparison (William’s). Results: At 7 days post–LHP injection, the maximum vessel length was observed to be 2.5±0.1 mm in the control animals (n=5), 2.0±0 mm in the 10 mg/kg A–3922 group (n=3, p<0.01 vs control), and 2.0±0.1 mm in the 30 mg/kg group(n=4, p<0.01), respectively. Twelve hours after LHP injection, VEGF was increased in the superior cornea 128.7±38.9 pg/mg wet weight in buffer control, 143.7±26.6 pg/mg wet weight in 10 mg/kg A–3922, 178.1±8.8 pg/mg wet weight in 30 mg/kg A–3922 (n=3). Conclusions: These results indicate that LHP–induced corneal NV was inhibited by pretreatment with A–3922, dihydrobenzofuran derivative. Dihydrobenzofuran derivatives may therefore be an appropriate pharmacological intervention for neovascular disorder, and its mechanisms will be discussed.Vessels growth was suppressed by A–3922 treatment.

Keywords: antioxidants • oxidation/oxidative or free radical damage