Role of NADPH Oxidase in Retinal Vascular Inflammation

• Published in: Investigative ophthalmology & visual science 2008-07, Vol.49 (7), p.3239-3244
• Main Authors: Al-Shabrawey, Mohamed, Rojas, Modesto, Sanders, Tammy, Behzadian, Ali, El-Remessy, Azza, Bartoli, Manuela, Parpia, Abdul Kader, Liou, Gregory, Caldwell, Ruth B
• Format: Article
• Language: English
• Subjects: Acetophenones - pharmacology; Animals; Biological and medical sciences; Blood-Retinal Barrier - drug effects; Cell Adhesion - drug effects; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Diabetic Retinopathy - complications; Down-Regulation; Endotoxemia - complications; Endotoxemia - metabolism; Enzyme Inhibitors - pharmacology; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Intercellular Adhesion Molecule-1 - metabolism; Leukocytes - drug effects; Leukostasis - etiology; Leukostasis - prevention & control; Lipopolysaccharides - pharmacology; Medical sciences; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; NADPH Oxidase 2; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - deficiency; NADPH Oxidases - metabolism; Ophthalmology; Reactive Oxygen Species - metabolism; Retinal Diseases - etiology; Retinal Diseases - metabolism; Retinal Vessels - metabolism; Up-Regulation; Vasculitis - etiology; Vasculitis - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.08-1755

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. 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. 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. 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.