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L.M. Cryan, D.J. Fitzgerald, C. O'Brien; Isoform Specific Disruption of the Cyclooxygenase Genes in Oxygen-induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2911.
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Purpose: Cyclooxygenase (COX)-1 and COX-2 and their products, the prostaglandins, have been implicated in several models of VEGF-dependent angiogenesis. Both selective and non-selective COX inhibitors have been shown to attenuate neovascularisation. We aim investigated the role of the COX enzymes in an oxygen-induced mouse model of retinopathy, using isoform specific knockout mice. Methods: Wildtype mice, COX-1 knockout mice (COX-1-/-) and COX-2 knockout mice (COX-2-/-) were exposed to 75% oxygen from postnatal day 7 (P7) to postnatal day 12 (P12) and then placed in normoxic conditions from P12 to P17/P18 . The resulting neovascularisation was quantified histologically and compared to age-matched controls. Immunohistochemistry confirmed the abscence or presence of each isoform in wildtype, COX-1-/- and COX-2-/- mice. Ocular prostacyclin, PGE2 and thromboxane production was determined by enzyme-immuno-assay Results: Immunohistochemistry confirmed the absence of COX-1 in COX-1-/- animals and the absence of COX-2 in COX-2-/- animals. Analysis of ocular prostaglandin levels revealed that prostacyclin was the most abundant, and is largely a product of the COX-1 isoform. Thromboxane was also produced by COX-1, whereas COX-1 and COX-2 both contributed to PGE2 production in the eye. Histological analysis revealed a similar increase in neovascularisation in wildtype, COX-1-/- and COX-2-/- mice when compared to age-matched normoxic controls (see table). Conclusions: Genetic disruption of either COX-1 or COX-2 failed to prevent retinal neovascularisation in these conditions. Inhibition of both isoforms may be required to prevent retinopathy. Alternatively, cyclooxygenase may not be essential for retinal angiogenesis, in contrast to other vascular beds. Avg. intravitreal nuclei/section for Wildtype, COX-1-/-, and COX-2-/- mice +/-SEM (10 sections/eye) View OriginalDownload SlideView OriginalDownload Slide
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