purpose. To clarify whether endogenous peroxisome proliferator-activated receptor γ (PPARγ) and its ligand, rosiglitazone, affect retinal leukostasis and the associated vascular leakage using an experimental diabetic model.

methods. Diabetes was induced in heterozygous PPARγ+/− mice and Brown Norway rats with an intraperitoneal streptozotocin (STZ) injection. Retinal leukostasis and leakage, quantified by concanavalin A (Con A) lectin perfusion labeling combined with a fluorophotometric dextran leakage assay, were investigated at 120 days in diabetic PPARγ+/− and wild-type mice and at 21 days in diabetic rats receiving rosiglitazone or the vehicle. The retinal protein expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, and the intercellular adhesion molecule (ICAM)-1 were investigated by means of the ELISA assay.

results. In the diabetic PPARγ+/− mice, retinal leukostasis and leakage were greater than in the diabetic wild-type mice. In addition retinal leukostasis and leakage were suppressed by treatment with rosiglitazone in experimental diabetic rats. ELISA analysis revealed that the upregulated ICAM-1 expression in the diabetic rat retina was reduced by rosiglitazone treatment.

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