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Customized Zebrafish Models of Hypoxia-Induced Neovascularization

The zebrafish embryo is an excellent model system for simulating retinopathy of prematurity. To help our global customers develop effective drugs to treat retinopathy of prematurity, Ace Therapeutics' researchers successfully develop a hypoxia-induced neovascularization model in zebrafish embryos to gain insight into the underlying pathophysiological mechanisms of retinopathy. Here, our ophthalmic pharmacologists will accompany you throughout the process to facilitate the smooth implementation of your projects.

Hypoxia Induced Neovascularization Model in Zebrafish Embryos

What Is Retinopathy of Prematurity?

Retinopathy of prematurity (ROP) is one of the most common causes of blindness in infants, most commonly seen in extremely premature infants before 30 weeks of gestation. It is characterized by vascular proliferation and fibrotic changes in the vitreous and retina. ROP formation consists of two stages: an initial stage of vascular loss and a second stage of vascular proliferation. Anti-VEGF drugs and cryotherapy/laser photocoagulation are commonly used clinical treatments. However, these treatments are not completely effective and may damage the immature retina. Therefore, an effective animal model is urgently needed to study the underlying mechanisms of ROP physiological and pathological angiogenesis and to develop potential anti-angiogenic therapies. The zebrafish has been proposed as an excellent model for simulating retinal neovascularization and ROP because of its transparency for easy in vivo observation; low cost; practicality; high fecundity; and the retinal vasculature is similar to many in humans.

Fig. 1. Development of the eye vasculature in zebrafish embryos. (Rezzola S, et al., 2016)

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ROP is a developmental disease, and the traditional animal model of oxygen-induced retinopathy (the ROP rat model) has certain limitations because animals are not always born prematurely. As one of the global leaders in the development of zebrafish eye disease models, in recent years, our ophthalmic pharmacologists have devoted themselves to developing a zebrafish model that fully simulates ROP--hypoxia-induced neovascularization model in zebrafish embryos.

This model can help you study the molecular mechanisms of ROP pathology. Importantly, it can rapidly assessment of efficacy and treatment with large sample sizes in a short period of time as a powerful tool.

Explore Ace Therapeutics' Hypoxia-Induced Neovascularization Model in Zebrafish Embryos

Ace Therapeutics' researchers induce two phases of ROP in zebrafish embryos by using CoCl₂ as a hypoxia inducer and the VEGF inducer GS4012 as an angiogenic agent. This was done with a follow-up period of up to 5 days.

Model characteristics: The number of vascular branches and buds in the central retinal vascular trunk of CoCl₂-treated zebrafish was significantly increased. At 2-4 days, retinal vascular characteristics were similar to stage 3 of human ROP. While subsequent use of the VEGF inducer GS4012 ensured the CoCl₂-induced cascade.

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To further verify the reliability of our model, our researchers use anti-VEGF monoclonal antibodies (bevacizumab and ranibizumab) for retinal neovascularization as positive compounds to judge whether our disease model can be reversed and use the following tools and methods to observe the characteristics of retinal neovascularization in zebrafish embryos under pathological conditions and endpoints, including but not limited to:

Confocal analysis.
Immunohistochemical analysis.
In vivo imaging analysis.
Molecular biology analysis.

Ace Therapeutics aims to provide a powerful analytical tool to help our global customers research to investigate molecular mechanisms of ROP pathology and conduct large-scale drug screens. If you are interested in our services or need more detailed information, please feel free to contact us. Our experienced scientists are ready to help you!

References

Rezzola S, Paganini G, Semeraro F, et al. Zebrafish (Danio rerio) embryo as a platform for the identification of novel angiogenesis inhibitors of retinal vascular diseases. Biochim Biophys Acta. 2016, 1862(7):1291-6.
Wu YC, Chang CY, Kao A, et al. Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity. PLoS One. 2015, 10(5):e0126750.

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