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T. L. Sanders, A. Tawfik, M. Al-Shabrawey; Decreased PPAR Expression in Oxygen-Induced Retinopathy: A Possible Role for NADPH Oxidase. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2627.
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Peroxisome proliferator-activated receptor gamma (PPAR γ) is a member of a ligand-activated nuclear receptor superfamily that has been shown to play a role in a variety of biological processes, including adipogenesis, glucose metabolism, inflammation and angiogenesis. PPAR γ ligands have been reported to inhibit experimental retinal, corneal and choroidal neovascularization. We have shown before the critical role played by reactive oxygen species (ROS) generated by NADPH oxidase in the pathogenesis of retinal neovascularization in oxygen-induced retinopathy (OIR). So, the goal of this study was to characterize the changes in the expression of PPAR γ during oxygen-induced retinopathy and to investigate whether NADPH oxidase plays any role in these changes.
Experimental retinal neovascularization has been developed by incubating a group of mice at postnatal day 7 (P7) in high oxygen (75%) for 5days, followed by 5-9 (P17-P21) days in normoxia. One group of the mice was treated with NADPH oxidase inhibitor; apocynin (intraperitoneal, 10 mg/kg) on P12-16 or PPAR γ agonist; rosiglitazone (intravitreal, 1 µl of 10mg/kg) on P12 and P14. Mice were then sacrificed on P17 and neovascularization was evaluated in retinal flat mounts labeled with Isolectin B4 and Texas red. We used a combination of immunolocalization and Western blotting techniques to analyze PPAR γ expression in relation to retinal angiogenesis on P13, P17 and P21.
Retinal expression of PPAR γ decreased in OIR as compared with the normal retina at P13 (2.2 + 0.3 vs 15.3 + 7, P< 0.05), P17 (1.7 + 0.26 vs 2.1 + 0.26) and P21 (1.58 + 0.1 vs 2.6 + 0.16 P< 0.05). PPAR γ level in retina was restored by apocynin treatment (2.7 + 0.44 vs1.7 + 0.26 in non treated group) and this was associated with the regression of retinal neovascularization. Furthermore, intravitreal injection of rosiglitazone reduced retinal neovacularization.
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