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M. A. Al-Shabrawey, T. L. Sanders, R. B. Caldwell; NAD(P)H Oxidase Regulates PPAR Expression in Models of Ischemic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4963.
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We have recently demonstrated that reactive oxygen species derived from NAD(P)H oxidase are important for retinal neovascularization in a model of oxygen-induced retinopathy (OIR) as well as microvascular dysfunction during diabetic retinopathy as indicated by leukostasis and breakdown of the blood-retinal barrier. Peroxisome Proliferator-Activated Receptor γ (PPAR γ)is a member of a ligand-activated nuclear receptor superfamily and plays a critical role in angiogenesis and inflammation. The goal of this study was to investigate the role of PPAR γ in ischemic retinopathy and whether NAD(P)H oxidase regulates its expression in retina.
Diabetes was induced in gp91phox +/+ and -/- mice with intraperitoneal injection of streptozotocin. One group of gp91+/+ mice was treated with apocynin (10mg/kg in drinking water). Expression of 12-Lipoxygnase (inflammatory mediator) and ICAM-1 (inflammatory marker) was investigated in retina of different groups with Western blotting and immunofluroscence. PPAR γ expression in retinal vessels was investigated in retinal sections from normal and 5 weeks diabetic mice using specific anti-PPAR γ antibody and isolectin B4 to label retinal vessels. PPAR γ expression was also investigated in retinal section from mice having OIR with or without apocynin treatment.
PPARγ is expressed in retinal vessels of normal animals. However, diabetes decreases PPARγ expression, and increases the expression of 12-lipoxygenase and ICAM-1. Inhibition of NAD(P)H oxidase by apocynin or deletion of gp91phox prevents diabetes-induced changes in the expression of PPARγ, 12-lipoxygenase and ICAM-1 in retina. Interestingly, PPARγ expression is also decreased in retina of mice with OIR and is restored by apocynin treatment.
Ischemic retinopathy is associated with a decrease in PPAR γ and increases in inflammatory mediator and marker 12-lipoxygenase and ICAM-1. NAD(P)H oxidase might be a key mediator of these changes.
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