944 NADPH Oxidase NOX2 facilitates retinal neovascularisation in a mouse model of oxygen-induced retinopathy

Abstract

Background: High blood pressure and diabetes co-exist in clinical practice. Both conditions increase the risk of small vessel damage in the kidney and eye and diabetic retinopathy remains a leading cause of vision impairment. The advanced stage of proliferative diabetic retinopathy is associated with pathological neovascularisation subsequent to an initial phase of pre-existing vessel loss or damage. Although current ophthalmic therapy is often effective, many patients continue to lose vision in spite of best care. Therefore, an understanding of the underlying mechanism may provide better treatment strategies. Study Design: Accumulating evidence implicates an oxidative stress-related enzyme NADPH oxidase in retinal neovascularisation, so we examined its contribution to neovascularisation in a mouse model of oxygen-induced retinopathy (OIR). Because Nox2 is the major isoform expressed in endothelial cells and involved in vessel growth, we compared the degree of retinal neovascularisation between Nox2-deficient (KO) and wildtype (WT) mice in OIR. Neonatal pups aged 7 days (P7) were placed in a hyperoxic chamber (75%O2) for 5 days to obliterate developing blood vessels, after which they were returned to room air for 5 days (P17). The avascular retina becomes hypoxic, which triggers neovascularisation. Results: Nox2 and VEGF gene expression was gradually elevated during the phase of neovascularisation and both responses were significantly reduced in Nox2 KO animals (see below figure).Conclusions: Nox2 is an important signalling mediator involved in retinal neovascularisation in OIR, possibly via VEGF. Our findings suggest an additional avenue for intervention to suppress neovascularisation associated with proliferative retinopathy.