naphthoquinones and Retinal-Neovascularization

Retinal neovascularization in retinopathy of prematurity (ROP) is the most common cause of blindness for children. Despite evidence that hypoxia inducible factor (HIF)-1α -VEGF axis is associated with the pathogenesis of ROP, the inhibitors of HIF-1α have not been established as a therapeutic target in the control of ROP pathophysiology. We investigated the hypothesis that degradation of HIF-1α as a master regulator of angiogenesis in hypoxic condition, using β-lapachone, would confer protection against hypoxia-induced retinopathy without affecting physiological vascular development in mice with oxygen-induced retinopathy (OIR), an animal model of ROP. The effects of β-lapachone were examined after intraocular injection in mice with OIR. Intraocular administration of β-lapachone resulted in significant reduction in hypoxia-induced retinal neovascularization without retinal toxicity or perturbation of developmental retinal angiogenesis. Our results demonstrate that HIF-1α-mediated VEGF expression in OIR is associated with pathological neovascularization, not physiological angiogenesis. Thus, strategies blocking HIF-1α in the developing eye in the pathological hypoxia could serve as a novel therapeutic target for ROP.

Topics: Animals; Apoptosis; Astrocytes; Cell Hypoxia; Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Injections, Intraocular; Mice, Inbred C57BL; Naphthoquinones; Oxygen; Proteolysis; Retina; Retinal Neovascularization; Transcription, Genetic; Vascular Endothelial Growth Factor A