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Anti-angiogenic effect of KH902 on retinal neovascularization
Fei Wang1, Yujing Bai, Wenzhen Yu
1Key Laboratory of Vision Loss and Restoration, Ministry of Education, Department of Ophthalmology, Peking University People's Hospital, Xizhimen South Street 11, Xi Cheng District, 100044, Beijing, China.
Insights
KH902 effectively inhibited angiogenesis in a mouse model of retinopathy of prematurity. This fusion protein shows promise for preventing retinal neovascularization in premature infants.
Area of Science:
- Ophthalmology
- Vascular Biology
- Pharmacology
Background:
- Retinopathy of prematurity (ROP) is a leading cause of blindness in premature infants, characterized by abnormal retinal blood vessel development.
- Vascular Endothelial Growth Factor (VEGF) plays a critical role in the pathogenesis of ROP.
Purpose of the Study:
- To evaluate the anti-angiogenic effects of KH902, a novel fusion protein targeting VEGF receptors, in an oxygen-induced retinopathy (OIR) mouse model.
- To assess KH902's potential as a therapeutic agent for ROP.
Main Methods:
- In vitro studies utilized human umbilical vein endothelial cells (HUVECs) to assess proliferation, migration, apoptosis, and tube formation.
- In vivo studies employed the C57BL/6 J OIR mouse model, with intravitreous injections of KH902.
- Retinal vascularization and leakage were quantified using fluorescein isothiocyanate (FITC)-dextran and Evans Blue perfusion.
Main Results:
- KH902 demonstrated dose-dependent inhibition of HUVEC proliferation, migration, and tube formation, while inducing apoptosis in vitro.
- In vivo, KH902 significantly reduced the retinal non-perfused area (from 34% to 19%) and leakage area (from 18% to 9%) in OIR mice.
Conclusions:
- KH902 exhibits potent anti-angiogenic properties both in vitro and in vivo.
- These findings support KH902 as a potential innovative therapeutic agent for preventing retinal neovascularization in ROP.
Purpose:
KH902 is a fusion protein derived from the extracellular domains of vascular endothelial growth factor (VEGF) receptors 1 and 2 and the Fc portion of immunoglobulin G1 (IgG1). Retinopathy of prematurity (ROP) is an eye disease that affects premature babies who have received intensive neonatal care, and the disorganization of retinal blood vessels may result in scarring and retinal detachment. This study was designed to examine the inhibitory effects of KH902 on mice with oxygen-induced retinopathy (OIR), one of the animal models of ROP.
Methods:
Human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and the C57BL/6 J OIR mouse model was used for an in vivo study. HUVECs were incubated with KH902 or a VEGF- and KH902-containing medium. Cell proliferation, migration, apoptosis, and tube formation were measured with BrdU incorporation, Transwell, flow cytometry, and Matrigel assays. C57BL/6 J mice were exposed to 75 % oxygen from postnatal day 7 (P7) to P12, after which the mice were brought to room air and intravitreously injected with KH902. At P18, the mice were perfused with fluorescein isothiocyanate (FITC)-dextran and Evans Blue, and flat-mounted retinas were used to measure the non-perfused and leakage areas. The data were analyzed with GraphPad Prism 5.0 software.
Results:
In vitro, KH902 dose-dependently inhibited HUVEC proliferation in general culture medium and in VEGF165-containing medium at different time points. Moreover, KH902 inhibited HUVEC migration and tube formation and induced HUVEC apoptosis. In vivo, an intravitreous injection of KH902 reduced the retinal non-perfused area from 34 % in the control group to 19 % in the treatment group and significantly reduced the retinal leakage area from 18 % to 9 %.
Conclusion:
KH902 had marked inhibitory effects on angiogenesis both in vitro and in vivo. These data suggest that KH902 could serve as an innovative pharmaceutical agent to prevent retinal neovascularization (NV) and as a strategy for the treatment of ROP.
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