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Redox mechanisms in pathological angiogenesis in the retina: roles for NADPH oxidase

journal contribution
posted on 2023-05-19, 10:51 authored by Chan, EC, Guei-Sheung LiuGuei-Sheung Liu, Dusting, GJ
Pathological angiogenesis in the retina is a leading cause of serious vision loss in potentially blinding eye diseases, including proliferative diabetic retinopathy, retinopathy of prematurity and the wet form of agerelated macular degeneration. Hypoxia is thought to be the driver of pathological angiogenesis, and transcription factors such as hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) are key mediators in these processes. Current treatments employ either laser photocoagulation or intravitreal injection of therapeutic antibodies for VEGF, in order to arrest the growth of leaky blood vessels in the avascular vitreous cavity and to restore visual acuity. However, all such therapeutic approaches are limited by low or variable efficacy, and the inconvenience, risk and financial burden of such treatments, which need to be given frequently. The lack of noninvasive and efficacious therapy has therefore driven the search for alternative strategies. We have been interested in the roles of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, which when produced intracellularly at low concentration can act as second messengers to regulate physiological and pathological angiogenesis. Accumulating evidence suggests NADPH oxidase-dependent ROS are involved in regulation of the angiogenic signalling pathways of HIF and VEGF. Suppressing pathological neovascularisation in the retina by manipulating such redox mechanisms appears to be an attractive and clinically translatable therapeutic strategy to treat proliferative neovascular eye diseases. Here we provide a brief overview of the roles of NADPH oxidase in the sensing and regulation processes involving HIF and VEGF that contribute to the development of pathological angiogenesis in the retina.

History

Publication title

Current Pharmaceutical Design

Volume

21

Issue

41

Pagination

5988-5998

ISSN

1381-6128

Department/School

Menzies Institute for Medical Research

Publisher

Bentham Science Publ Ltd

Place of publication

Po Box 1673, Hilversum, Netherlands, 1200 Br

Rights statement

© 2015 Bentham Science Publishers

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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