Beta‐lapachone inhibits pathological retinal neovascularization in oxygen‐induced retinopathy via regulation of HIF‐1α

Journal of Cellular and Molecular Medicine

Sung Wook Park⁴  Jin Hyoung Kim⁴  Ko-Eun Kim¹  Moon Hee Jeong³  Hyunsung Park⁵  Bongju Park⁵  Young-Ger Suh²  Woo Jin Park³ 

[1] Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea;College of Pharmacy, Seoul National University, Seoul, Korea;Global Research Laboratory and Life Sciences Concentration, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea;Fight against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea;Department of Life Science, University of Seoul, Seoul, Korea

关键词: β‐lapachone;    hypoxia‐induced factor 1‐α;    oxygen‐induced retinopathy;    retinal neovascularization;    retinopathy of prematurity;    vascular endothelial growth factor;   

DOI  :  10.1111/jcmm.12235

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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