Abstract
Abstract: :
Purpose: Choroidal neovascularization is a serious pathological feature of the exudative form of age–related macular degeneration (AMD). Cyclooxygenase–2 (COX–2) has been associated with neovascularization (potentially through VEGF upregulation) in conjunction with various retinopathies. Here the antiangiogenic effects of a novel COX–2 selective inhibitor, lumiracoxib, are characterized in the Brown Norway rat CNVM model. Methods: Beginning on Day 0, 12 male rats received daily oral gavage dosages of 20 mg/kg lumiracoxib in a 0.5% (w/v) suspension of Blanose® sodium carboxymethylcellulose (CMC). A second group of 12 control rats received the 0.5% CMC suspension only. On Day 7, a series of 8 green–diode laser (532 nm, 0.05 seconds, 75 µm, and 90 mW) photocoagulation sites were placed concentrically around the optic disk to induce CNVMs. Fundus and fluorescein angiography (FA) photography occurred just prior to euthanasia on Day 35. Eyes were then processed for histopathologic analysis with light microscopy. Results: Comparisons of the two groups, with fundus and FA photography, did not reveal any obvious differences in CNVM development. However, pigmented macrophages, which typically infiltrate the retina within CNVM sites, were noticeably absent in the lumiracoxib–treated eyes. Histopathologic analysis demonstrated that the mean CNVM thickness was significantly less in the lumiracoxib–treated animals (38 ± 19 µm) compared with the control animals (54 ± 20 µm; p<0.0001). Both groups experienced an equivalent weight gain of 3–4% during the study. Conclusions:Systemic administration of the COX–2 selective inhibitor lumiracoxib results in a significant reduction in CNVM development in the rat laser–trauma model and thus may be beneficial as an inhibitor of CNVM formation in exudative AMD.
Keywords: drug toxicity/drug effects • choroid: neovascularization • age–related macular degeneration