COX-2 protects against thrombosis of the retinal vasculature in a mouse model of proliferative retinopathy.
Item Type:Journal Article
Citation:Cryan LM, Pidgeon GP, Fitzgerald DJ, O'Brien CJ. `COX-2 protects against thrombosis of the retinal vasculature in a mouse model of proliferative retinopathy? in Molecular Vision, 12, 2006, pp 405 - 414
COX-2 protects against thrombosis of the retinal vasculature in a mouse model of proliferative retinopathy.pdf (Published (publisher's copy) - Peer Reviewed) 307.1Kb
Purpose: Cyclooxygenases (COX-1 and COX-2) and prostaglandins regulate angiogenesis in several settings, including cancer and ischemia. In the eye, both selective inhibitors of COX-2 and nonselective COX inhibitors are reported to suppress ischemia-related retinal angiogenesis. Such studies however, may be confounded by the nonspecific effects of inhibitors. Methods: Mice lacking either the COX-1 (COX-1-/-) or COX-2 isoform (COX-2-/-) were employed in a model of oxygeninduced retinopathy. Vascular responses were examined by histology, isolectin B4 staining of the abluminal endothelium, and retinal fluorescein angiography. Results: There was an increase in intravitreal endothelial nuclei in hyperoxia-treated mice compared to normoxic controls irrespective of the genotype. Quantitative analysis of fluorescein-perfused and isolectin B4-stained retinal angiograms at postnatal day 18 (P18) revealed similar global levels of neovascular tufts in hyperoxia-treated wild-type, COX-1-/-, and COX-2-/- mice. However, hyperoxia-treated COX-2-/- mice had increased areas of retinal nonperfusion (29.2?1.9 compared to 16.3?2.7; n=6; p<0.001). COX-1 disruption had no effect (15.6?2.6; n=8). Platelet deposition within retinal vessels was increased in hyperoxia-treated COX-2-/- mice (p<0.05). Conclusions: Genetic disruption of a single COX isoform is not sufficient to prevent oxygen-induced retinopathy. COX- 2 protects retinal vessels from thrombosis, limiting the area of retinal nonperfusion in oxygen-induced retinopathy.
Author: PIDGEON, GRAHAM
Type of material:Journal Article
Series/Report no:Molecular Vision
Availability:Full text available