COX-2 protects against thrombosis of the retinal vasculature in amouse model of proliferative retinopathy

[摘要] Purpose: Cyclooxygenases (COX-1 and COX-2) and prostaglandinsregulate angiogenesis in several settings, including cancer andischemia. In the eye, both selective inhibitors of COX-2 andnonselective COX inhibitors are reported to suppress ischemia-relatedretinal angiogenesis. Such studies however, may be confounded by thenonspecific effects of inhibitors.Methods: Mice lacking either the COX-1 (COX-1-/-) or COX-2isoform (COX-2-/-) were employed in a model of oxygen-inducedretinopathy. Vascular responses were examined by histology, isolectin B4staining of the abluminal endothelium, and retinal fluoresceinangiography.Results: There was an increase in intravitreal endothelial nuclei inhyperoxia-treated mice compared to normoxic controls irrespective of thegenotype. Quantitative analysis of fluorescein-perfused and isolectinB4-stained retinal angiograms at postnatal day 18 (P18) revealed similarglobal levels of neovascular tufts in hyperoxia-treated wild-type,COX-1-/-, and COX-2-/- mice. However, hyperoxia-treatedCOX-2-/- mice had increased areas of retinal nonperfusion(29.2±1.9 compared to 16.3±2.7; n=6; p<0.001). COX-1disruption had no effect (15.6±2.6; n=8). Platelet deposition withinretinal vessels was increased in hyperoxia-treated COX-2-/- mice(p<0.05).Conclusions: Genetic disruption of a single COX isoform is notsufficient to prevent oxygen-induced retinopathy. COX-2 protects retinalvessels from thrombosis, limiting the area of retinal nonperfusion inoxygen-induced retinopathy.

[学科分类] 生物化学/生物物理