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
age-related 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.