Aucuba japonica extract inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy, with its bioactive components preventing VEGF-induced retinal vascular hyperpermeability

Neovascularization in the retina is common pathophysiology of diabetic retinal microvasculopathy and exudative macular degeneration. Our study assessed the inhibitory activity of an ethanol-based extract of Aucuba japonica (AJE) on abnormal angiogenesis in the retina with a hyperoxia-induced neovascular retinopathy model. The inhibitory effects of aucubin, quercetin, and kaempferol, bioactive compounds, from A. japonica, on retinal vascular hyperpermeability were also examined. On the 7th postnatal day (P7), the C57BL/6 pups were exposed to a hyperoxic environment with 75% oxygen to develop the experimental angiogenesis in retinas. On the 12th postnatal day (P12), the pups were then returned to the normal atmospheric pressure of oxygen. From P12 to P16, the administration was intraperitoneal. The dose per day was 250 mg per kg weight. Retinal neovascularization was measured with retinal flat mounts prepared on P17. We also measured the vascular leakage mediated by the vascular endothelial growth factor (VEGF) in retinas. Mice treated with AJE had markedly smaller neovascular lesions, in comparison with vehicle-administered mice. AJE downregulated the expression of both VEGF protein and mRNA. In addition, aucubin, quercetin, and kaempferol ameliorated VEGF-induced retinal vascular leakage. The results of our study suggest that AJE is a potent antiangiogenic substance. AJE could also serve as a therapeutic agent for abnormal growth of vessels in the retina in patients with ischemic retinopathy. The bioactive compounds of AJE may be responsible for its antiangiogenic abilities.

Keywords: Aucuba japonica; angiogenesis; functional food; retinal neovascularization.