ORAL ADMINISTRATION OF LUMIRACOXIB REDUCES CHOROIDAL NEOVASCULAR MEMBRANE DEVELOPMENT IN THE RAT LASER-TRAUMA MODEL

Abstract

To determine whether lumiracoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that exhibits anti-inflammatory and antiangiogenic properties, can inhibit experimental choroidal neovascular membrane (CNVM) development induced by focal laser trauma in a well-characterized Brown Norway rat CNVM model. Over a 35-day period, 24 rats received daily oral gavage dosages of 20 mg/kg lumiracoxib in a 0.5% (w/v) suspension of sodium carboxymethylcellulose (CMC), while a control group received the 0.5% CMC suspension only. After 7 days, eight laser photocoagulation sites were placed concentrically around the optic disk to induce CNVMs. Thirty-five days later, fundus photography and fluorescein angiography (FA) were performed and eyes were processed for histopathologic analysis. Masked FA grading of lesion sites revealed a small, but statistically significant difference (P<0.0001) in late stage staining intensity and leakage between the mean group scores of treated (1.4) and control (1.7) eyes. Histopathologic analysis demonstrated that the mean CNVM thickness +/- SD of 38 +/-19 microm (n=24 eyes, 175 photocoagulation sites) in the lumiracoxib-treated animals was reduced by 30% (P<0.001) compared to the CNVM mean thickness+/- SD of 54+/- 20 microm (n=24 eyes, 171 photocoagulation sites) in the control animals. Systemic administration of the selective COX-2 inhibitor lumiracoxib results in a partial but significant reduction in CNVM development in the rat laser-trauma model and thus may be clinically beneficial as a potential inhibitor of CNVM formation in exudative age-related macular degeneration.