title: A potential role for angiopoietin 2 in the regulation of the blood-retinal barrier in diabetic retinopathy.
abstract: OBJECTIVE
  Although VEGF has been identified as an important mediator of the blood-retinal barrier alteration in diabetic retinopathy, the hypothesis for this study was that that other molecules, including the angiopoietins (Ang-1 and -2), may play a role. The expression of angiopoietins was analyzed in an animal model of diabetic retinopathy, and the role of Ang-2 in the regulation of diabetes-induced alterations of vascular permeability was characterized.
  
  
  METHODS
  Diabetes was induced in rats, and human retinal endothelial cells (HRECs) were grown in media with 5.5 or 30.5 mM glucose. Levels of Ang-1 and -2 mRNA and protein were analyzed. Fluorescence-based assays were used to assess the effect of Ang-2 on vascular permeability in vivo and in vitro. The effect of Ang-2 on VE-cadherin function was assessed by measuring the extent of tyrosine phosphorylation.
  
  
  RESULTS
  Ang-2 mRNA and protein increased in the retinal tissues after 8 weeks of diabetes and in high-glucose-treated cells. Intravitreal injection of Ang-2 in rats produced a significant increase in retinal vascular permeability. Ang-2 increased HREC monolayer permeability that was associated with a decrease in VE-cadherin and a change in monolayer morphology. High glucose and Ang-2 produced a significant increase in VE-cadherin phosphorylation. CONCLUSIONS; Ang-2 is upregulated in the retina in an animal model of diabetes, and hyperglycemia induces the expression of Ang-2 in isolated retinal endothelial cells. Increased Ang-2 alters VE-cadherin function, leading to increased vascular permeability. Thus, Ang-2 may play an important role in increased vasopermeability in diabetic retinopathy.
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
authors.forename: Sampathkumar
authors.initials: S
authors.lastname: Rangasamy
authors.forename: Ramprasad
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Joann
authors.initials: J
authors.lastname: Maestas
authors.forename: Paul G
authors.initials: PG
authors.lastname: McGuire
authors.forename: Arup
authors.initials: A
authors.lastname: Das
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000502:physiology*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation; D000099152:Cadherin 5
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015703:Antigens, CD; D015820:Cadherins; D005947:Glucose; D012333:RNA, Messenger; D014443:Tyrosine; D000099152:Cadherin 5; C467629:Angpt1 protein, rat