Effects of Peroxisome Proliferator-Activated Receptor γ and Its Ligand on Blood–Retinal Barrier in a Streptozotocin-Induced Diabetic Model

Abstract

An endogenous pathway involving PPARgamma provides protection against retinal leukostasis and retinal leakage in diabetes and treatment with PPARgamma specific ligands inhibits retinal leukostasis and retinal leakage in diabetic rats.

Suppression of Retinal Peroxisome Proliferator-Activated Receptor γ in Experimental Diabetes and Oxygen-Induced Retinopathy: Role of NADPH Oxidase

“…Because vascular inflammation is crucial in the pathogenesis of vascular dysfunction, such as hyperpermeability 26 and neovascularization 27 associated with diabetic or ischemic retinopathy, we suggest that PPAR␥ may exert its protective effect by way of an anti-inflammatory pathway. This suggestion is consistent with the recent report by Muranaka et al, 33 who showed the inhibition of ICAM-1 expression, leukocyte adhesion, and retinal vascular leakage in experimental diabetes by the PPAR␥ agonist rosiglitazone and the increase in the same parameters by deletion of the gene encoding PPAR␥. Moreover, rosiglitazone has been shown to inhibit retinal neovascularization in OIR by a mechanism downstream from VEGF.…”

“…Synthetic PPAR␥ agonists such as pioglitazone and rosiglitazone increase insulin sensitivity, modify lipid profiles, decrease blood pressure, and reduce biomarkers of inflammation. 30 -32 Previous work has shown that the PPAR␥ signaling pathway inhibits diabetes-induced vascular injury in retina 33 and kidney 34 through a mechanism involving the inhibition of leukocyte adhesion. The anti-inflammatory effect of PPAR␥ has been shown to be mediated through the inhibition of the transcription factor nuclear factor (NF)〉, which plays a crucial role in inflammation.…”

Size-selective opening of the blood–brain barrier by targeting endothelial sphingosine 1–phosphate receptor 1

“…Retinal tracer leakage experiments were performed as described (51). Under deep isoflurane anesthesia, 3-kDa dextran-TMR (50 μg/g) was injected intravenously.…”

Triamcinolone acetonide protects the rat retina from STZ-induced acute inflammation and early vascular leakage

“…Its activation is closely connected with other proinflammatory factors, including tumor necrosis factor (TNF)-α or intracellular adhesion molecule-1 (ICAM-1) ( Bhatia and Moochhala, 2004;Rojas-Cartagena et al, 2005;Muranaka et al, 2006;Zhang et al, 2006); together, they are central in diabetes- Life Sciences 81 (2007) 1167 -1173 www.elsevier.com/locate/lifescie induced vascular pathophysiology. Furthermore, their activation and reciprocal regulation might be controlled by a transcriptional factor, nuclear factor (NF)-kB (Ishii et al, 2004;Shishodia and Aggarwal, 2004;Maeng et al, 2006).…”