Effects of peroxisome proliferator-activated receptor gamma and its ligand on blood-retinal barrier in a streptozotocin-induced diabetic model.

Abstract

PURPOSE:

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

METHODS:

Diabetes was induced in heterozygous PPARgamma+/- 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 PPARgamma+/- 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 PPARgamma+/- 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 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.

• Authors: Kimimasa Muranaka, Yasuo Yanagi, Yasuhiro Tamaki, Tomohiko Usui, Naoto Kubota, Aya Iriyama, Yasuo Terauchi, Takashi Kadowaki, Makoto Araie
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 47 Issue 10 Pg. 4547-52 (Oct 2006) ISSN: 0146-0404 [Print] United States
• PMID: 17003451 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Ligands
• PPAR gamma
• Thiazolidinediones
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• vascular endothelial growth factor A, rat
• Rosiglitazone
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Blood Glucose (analysis)
• Blood-Retinal Barrier (drug effects)
• Capillary Permeability
• Diabetes Mellitus, Experimental (drug therapy, metabolism, pathology)
• Diabetic Retinopathy (drug therapy, metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Fluorophotometry
• Immunoenzyme Techniques
• Intercellular Adhesion Molecule-1 (metabolism)
• Leukocytes (physiology)
• Leukostasis (metabolism, prevention & control)
• Ligands
• Male
• Mice
• Mice, Inbred C57BL
• PPAR gamma (deficiency, physiology)
• Rats
• Rats, Inbred BN
• Retinal Vessels (physiology)
• Rosiglitazone
• Thiazolidinediones (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation
• Vascular Endothelial Growth Factor A (metabolism)