title: Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2 diabetes mellitus model.
abstract: OBJECTIVE
  To examine the expression of high mobility group box-1 (HMGB-1) and intercellular adhesion molecule-1 (ICAM-1) in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier (BRB) and blood-brain barrier (BBB) in a rat model of type 2 diabetes.
  
  
  METHODS
  The type-2 diabetes mellitus (DM) model was established with a high-fat and high-glucose diet combined with streptozotocin (STZ). Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection (P<0.01). The serum levels of fasting insulin, Insulin resistance homeostatic model assessment (IRHOMA), total cholesterol (TC), total triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the DM rats significantly higher than those in the controls (allP<0.01). HMGB-1 (0.96±0.03,P<0.01) and ICAM-1 (0.76±0.12,P<0.05) levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1 (0.83±0.13,P<0.01) and ICAM-1 (1.15±0.08,P<0.01) levels in the hippocampal tissues in the DM rats were also significantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls (P<0.01). However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats.
  
  
  CONCLUSIONS
  BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China; University Hospital of Hubei University for Nationalities, Enshi 445000, Hubei Province, China.
authors.forename: Rui-Jin
authors.initials: RJ
authors.lastname: Ran
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Zheng
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Du
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China.
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China.
authors.forename: Shen-Yin
authors.initials: SY
authors.lastname: Zhu
keywords: blood-brain barrier; blood-retinal barrier; diabetes mellitus; high mobility group box-1 protein; permeability; rats