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Updated: May 3, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Beta-lapachone inhibits pathological retinal neovascularization in oxygen-induced retinopathy via regulation of
Sung Wook Park1, Jin Hyoung Kim, Ko-Eun Kim
1Fight against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
Insights
Degrading hypoxia-inducible factor-1α (HIF-1α) with β-lapachone reduced pathological retinal neovascularization in retinopathy of prematurity (ROP) models. This targeted approach offers a potential new therapy for preventing childhood blindness caused by ROP.
Area of Science:
- Ophthalmology
- Vascular Biology
- Pharmacology
Background:
- Retinopathy of prematurity (ROP) causes childhood blindness due to retinal neovascularization.
- The hypoxia-inducible factor (HIF)-1α -VEGF pathway is implicated in ROP pathogenesis.
- HIF-1α inhibitors are not yet established therapeutic targets for ROP.
Purpose of the Study:
- To investigate if β-lapachone, by degrading HIF-1α, protects against hypoxia-induced retinopathy.
- To determine if this protection occurs without disrupting normal retinal vascular development.
Main Methods:
- Utilized the oxygen-induced retinopathy (OIR) mouse model, an established animal model for ROP.
- Administered β-lapachone via intraocular injection in OIR mice.
- Assessed retinal neovascularization, toxicity, and developmental angiogenesis.
Main Results:
- Intraocular β-lapachone significantly reduced hypoxia-induced retinal neovascularization in OIR mice.
- No observed retinal toxicity or perturbation of physiological retinal angiogenesis.
- Demonstrated that HIF-1α-mediated VEGF expression is linked to pathological, not physiological, angiogenesis in OIR.
Conclusions:
- Targeting HIF-1α degradation with agents like β-lapachone is a promising therapeutic strategy for ROP.
- Blocking HIF-1α in the context of pathological hypoxia in the developing eye may prevent ROP-related blindness.
- This approach differentiates between pathological and physiological angiogenesis, offering a specific therapeutic window.
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.
