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NADPH Oxidase in Choroidal Neovascularization

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Studies on Retinal and Choroidal Disorders

Abstract

Choroidal neovascularization (CNV) occurs in a variety of chorioretinal diseases including age-related macular degeneration (AMD) and is the major cause of severe visual loss in patients with AMD. Oxidative stress has been thought to play an important role in the development of CNV, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as one of the major intracellular sources of reactive oxygen species (ROS) in the vascular system is a logical candidate as a central player. In this chapter, we review the role of p22phox, an integral subunit in the NADPH oxidase complex, in the mouse eye in relation to CNV. We show that p22phox is expressed in the retinal pigment epithelial (RPE) cells and inner retinal neurons and that a small-interfering RNA (siRNA) designed against p22phox efficiently reduces the expression of the protein in the retina when delivered by means of recombinant adeno-associated virus (AAV) vector. Vector treatment inhibited CNV in the mouse when delivered into the subretinal space where RPE cells were transduced. These results suggest that NADPH oxidase-mediated ROS production in RPE cells may play an important role in the pathogenesis of neovascular AMD, and that this pathway may represent a new target for its therapeutic intervention.

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Acknowledgments

We acknowledge NIH grants EY13729, EY11123, EY08571, and grants from the Macular Vision Research Foundation, Foundation Fighting Blindness, Juvenile Diabetes Research Foundation, and Research to Prevent Blindness, Inc. American Diabetes Association for partial support of this work. W.W.H. and the University of Florida have a financial interest in the use of AAV therapies, and own equity in a company (AGTC Inc.) that might, in the future, commercialize some aspects of this work. We thank Mike Daniel for help with statistic analysis, and Clay Smith for help with Western blot analysis.

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Li, Q., Verma, A., Dinculescu, A., Lewin, A.S., Hauswirth, W.W. (2012). NADPH Oxidase in Choroidal Neovascularization. In: Stratton, R., Hauswirth, W., Gardner, T. (eds) Studies on Retinal and Choroidal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-61779-606-7_14

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