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A. Ottlecz, S.X. Zhang, J.–X. Ma, G.N. Lambrou; Lumiracoxib inhibits retinal neovascularization in a rat model of oxygen–induced retinopathy . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4037.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: This study used a rat model of oxygen–induced ischemic retinopathy (OIR) to evaluate the effects of oral lumiracoxib, a COX–2 inhibitor, on retinal neovascularization (NV). Methods: OIR was induced in Brown–Norway neonates by exposing 7–day old rats to 75 ± 2% O2 for 5 days followed by 7 days in room air. Doses of lumiracoxib (1, 10 and 50 mg/kg) or its vehicle, 0.5% carboxymethylcellulose (CMC), were administered once daily by gavage to the hyperoxia–exposed rats between postnatal days 12–18. Another group of animals received one single intravitreal injection of the plasminogen kringle 5 (K5) peptide, used as a positive control, in one eye (10 µg in 3 µl phosphate buffer saline). The contra–lateral eye received the same volume of vehicle (PBS) as a negative control. At day 19, animals were sacrificed for analysis of retinal NV by fluorescein retinal angiography and histopathology (counting pre–retinal neovascular cells on sagittal sections). Results: Lumiracoxib 10 mg/kg and 50 mg/kg significantly decreased the number of pre–retinal neovascular endothelial cells. Compared with placebo–treated rats, those receiving 10 mg/kg lumiracoxib (n=13) had a 23% decrease in pre–retinal neovascular endothelial cells (p=0.0014) while those receiving 50 mg/kg lumiracoxib (n=12) had a 38% decrease (p<0.00005). There was no reduction in the number of pre–retinal neovascular endothelial cells in rats treated with 1 mg/kg COX–2 inhibitor. The positive control, intravitreal K5, showed a significant reduction in pre–retinal NV (n=5; p=0.011) compared with the phosphate buffered saline control (n=5). Conclusions: Oral lumiracoxib significantly reduced retinal NV. These data confirm previous findings indicating that COX–2 plays an important role in angiogenesis. COX–2 inhibition may, therefore, serve as a valuable therapeutic tool in the treatment of ocular diseases with retinal NV.
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