title: Reactive oxygen species, Nox and angiotensin II in angiogenesis: implications for retinopathy.
abstract: Pathological angiogenesis is a key feature of many diseases including retinopathies such as ROP (retinopathy of prematurity) and DR (diabetic retinopathy). There is considerable evidence that increased production of ROS (reactive oxygen species) in the retina participates in retinal angiogenesis, although the mechanisms by which this occurs are not fully understood. ROS is produced by a number of pathways, including the mitochondrial electron transport chain, cytochrome P450, xanthine oxidase and uncoupled nitric oxide synthase. The family of NADPH oxidase (Nox) enzymes are likely to be important given that their primary function is to produce ROS. Seven isoforms of Nox have been identified named Nox1-5, Duox (dual oxidase) 1 and Duox2. Nox1, Nox2 and Nox4 have been most extensively studied and are implicated in the development of conditions such as hypertension, cardiovascular disease and diabetic nephropathy. In recent years, evidence has accumulated to suggest that Nox1, Nox2 and Nox4 participate in pathological angiogenesis; however, there is no clear consensus about which Nox isoform is primarily responsible. In terms of retinopathy, there is growing evidence that Nox contribute to vascular injury. The RAAS (renin-angiotensin-aldosterone system), and particularly AngII (angiotensin II), is a key stimulator of Nox. It is known that a local RAAS exists in the retina and that blockade of AngII and aldosterone attenuate pathological angiogenesis in the retina. Whether the RAAS influences the production of ROS derived from Nox in retinopathy is yet to be fully determined. These topics will be reviewed with a particular emphasis on ROP and DR.
authors: Department of Immunology, Central Clinical School, Monash University, 99 Commercial Road, Alfred Medical Research and Education Precinct (AMREP), Alfred Centre, Melbourne, Victoria 3004, Australia. Jennifer.wilkinson-berka@monash.edu
authors: Jennifer L
authors: JL
authors: Wilkinson-Berka
authors: Indrajeetsinh
authors: I
authors: Rana
authors: Roksana
authors: R
authors: Armani
authors: Alex
authors: A
authors: Agrotis
mesh_terms: D000804:Angiotensin II; D000818:Animals; D003930:Diabetic Retinopathy / Q000209:etiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature; D007249:Inflammation / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D023421:Models, Animal; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D012084:Renin-Angiotensin System; D012160:Retina / Q000502:physiology; D012178:Retinopathy of Prematurity / Q000209:etiology*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000804:Angiotensin II; C056558:CYBB protein, human; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C498910:NOX4 protein, human