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(Investigative Ophthalmology and Visual Science. 2006;47:4547-4552.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-1432
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Effects of Peroxisome Proliferator-Activated Receptor {gamma} and Its Ligand on Blood–Retinal Barrier in a Streptozotocin-Induced Diabetic Model

Kimimasa Muranaka,1 Yasuo Yanagi,1 Yasuhiro Tamaki,1 Tomohiko Usui,1 Naoto Kubota,2 Aya Iriyama,1 Yasuo Terauchi,2 Takashi Kadowaki,3 and Makoto Araie1

1From the Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan; the 2Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan; and the 3Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

PURPOSE. To clarify whether endogenous peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its ligand, rosiglitazone, affect retinal leukostasis and the associated vascular leakage using an experimental diabetic model.

METHODS. Diabetes was induced in heterozygous PPAR{gamma}+/– 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 PPAR{gamma}+/– 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)-{alpha}, and the intercellular adhesion molecule (ICAM)-1 were investigated by means of the ELISA assay.

RESULTS. In the diabetic PPAR{gamma}+/– 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 PPAR{gamma} provides protection against retinal leukostasis and retinal leakage in diabetes and treatment with PPAR{gamma} specific ligands inhibits retinal leukostasis and retinal leakage in diabetic rats.




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