Title:Redox mechanisms in pathological angiogenesis in the retina: roles for NADPH oxidase
Volume: 21
Issue: 41
Author(s): Elsa C. Chan, Guei-Sheung Liu and Gregory J. Dusting
Affiliation:
Keywords:
Retinal neovascularisation, NADPH oxidase, VEGF, HIF, hypoxia, nanomedicine.
Abstract: 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.
