COX-2 protects against thrombosis of the retinal vasculature in a mouse model of proliferative retinopathy.
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 - 414Download Item:
Abstract:
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.
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http://people.tcd.ie/pidgeongDescription:
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Author: PIDGEON, GRAHAM
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Molecular VisionType of material:
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Molecular Vision12
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