title: Effects of peroxisome proliferator-activated receptor gamma and its ligand on blood-retinal barrier in a streptozotocin-induced diabetic model.
abstract: OBJECTIVE
  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.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Muranaka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Usui
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Aya
authors.initials: A
authors.lastname: Iriyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D015590:Fluorophotometry; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D018921:Leukostasis / Q000378:metabolism / Q000517:prevention & control; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000172:deficiency / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D012171:Retinal Vessels / Q000502:physiology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C467498:vascular endothelial growth factor A, rat; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1