Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 18, Issue 5, Pages 875-884Publisher
WILEY
DOI: 10.1111/jcmm.12235
Keywords
-lapachone; hypoxia-induced factor 1-; oxygen-induced retinopathy; retinal neovascularization; retinopathy of prematurity; vascular endothelial growth factor
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Funding
- Seoul National University Research Grant [800-20130338]
- Seoul National University Hospital Research Fund [03-2013-0070]
- Pioneer Research Program of NRF/MEST [2012-0009544]
- Bio-Signal Analysis Technology Innovation Program of NRF/MEST [2009-0090895]
- NRF/MEST [2009-0085747]
- Global Research Laboratory Program of NRF/MEST [M6-0605-00-0001]
- National Research Foundation of Korea [2009-0085747] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Retinal neovascularization in retinopathy of prematurity (ROP) is the most common cause of blindness for children. Despite evidence that hypoxia inducible factor (HIF)-1 -VEGF axis is associated with the pathogenesis of ROP, the inhibitors of HIF-1 have not been established as a therapeutic target in the control of ROP pathophysiology. We investigated the hypothesis that degradation of HIF-1 as a master regulator of angiogenesis in hypoxic condition, using -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 -lapachone were examined after intraocular injection in mice with OIR. Intraocular administration of -lapachone resulted in significant reduction in hypoxia-induced retinal neovascularization without retinal toxicity or perturbation of developmental retinal angiogenesis. Our results demonstrate that HIF-1-mediated VEGF expression in OIR is associated with pathological neovascularization, not physiological angiogenesis. Thus, strategies blocking HIF-1 in the developing eye in the pathological hypoxia could serve as a novel therapeutic target for ROP.
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