title: Role of NADPH oxidase in retinal vascular inflammation.
abstract: OBJECTIVE
  In another study, it was demonstrated that NADPH oxidase-derived reactive oxygen species (ROS) are important for ischemia-induced increases in vascular endothelial growth factor (VEGF) and retinal neovascularization. Diabetes-induced increases in retinal ROS, VEGF expression, and vascular permeability are accompanied by increases in the NADPH oxidase catalytic subunit NOX2 within the retinal vessels. The goal of this study was to evaluate the potential role of NOX2 and NADPH oxidase activity in the development of retinal vascular inflammation.
  
  
  METHODS
  Studies were performed in wild-type mice, mice lacking NOX2, and mice treated with the NADPH oxidase inhibitor apocynin in models of endotoxemia and streptozotocin-induced diabetes. Intracellular adhesion molecule (ICAM)-1 expression was determined by Western blot analysis. Leukocyte adhesion was assessed by labeling adherent leukocytes with concanavalin A. Vascular permeability was assessed by extravasation of FITC-conjugated albumin. ROS production was determined by dichlorofluorescein imaging.
  
  
  RESULTS
  Both endotoxemia- and diabetes-induced increases in ICAM-1 expression and leukostasis were significantly inhibited by deletion of NOX2, indicating that this enzyme is critically involved in both conditions. Moreover, apocynin treatment and deletion of NOX2 were equally effective in preventing diabetes-induced increases in ICAM-1, leukostasis, and breakdown of the blood-retinal barrier, suggesting that NOX2 is primarily responsible for these early signs of diabetic retinopathy.
  
  
  CONCLUSIONS
  These data suggest that NOX2 activity has a primary role in retinal vascular inflammation during acute and chronic conditions associated with retinal vascular inflammatory reactions. Targeting this enzyme could be a novel therapeutic strategy for treatment of the retinopathies associated with vascular inflammation.
authors: Oral Biology and Anatomy, School of Dentistry, Medical College of Georgia, Augusta, Georgia 30912, USA. malshabrawey@mcg.edu
authors: Mohamed
authors: M
authors: Al-Shabrawey
authors: Modesto
authors: M
authors: Rojas
authors: Tammy
authors: T
authors: Sanders
authors: Ali
authors: A
authors: Behzadian
authors: Azza
authors: A
authors: El-Remessy
authors: Manuela
authors: M
authors: Bartoli
authors: Abdul Kader
authors: AK
authors: Parpia
authors: Gregory
authors: G
authors: Liou
authors: Ruth B
authors: RB
authors: Caldwell
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000150:complications; D015536:Down-Regulation; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D018921:Leukostasis / Q000209:etiology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012164:Retinal Diseases / Q000209:etiology* / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism*; D015854:Up-Regulation; D014657:Vasculitis / Q000209:etiology* / Q000378:metabolism
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; C056165:acetovanillone; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases