Zebrafish Retinal Vascular Disease Models

Visual deficits affect a large proportion of humans, have a significant negative impact on quality of life, and cause a significant financial burden. The wide variety of visual impairments and the large number of genetic mutations require flexible animal model systems to study possible causes and treatments for blinding conditions. Pathological retinal angiogenesis contributes significantly to irreversible causes of visual impairment at all ages, such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and age-related macular degeneration (AMD).

The zebrafish has a more distant phylogeny from humans than rodents, but it shares 82% of orthologs of human disease-related genes. Although zebrafish eyes are very small compared to humans, they contain almost all the basic structures of the human eye. Zebrafish eyes are structurally and functionally similar to humans, and zebrafish have been used to study genetic and environmental eye diseases, including myopia, glaucoma, retinitis pigmentosa, ciliopathies, albinism, and diabetes. Due to the striking similarities in the vasculature between zebrafish and humans, zebrafish embryos have been used to identify genes and mechanisms involved in pathological retinal angiogenesis.

Fig.1 The adult zebrafish has a complex retinal vasculature.

Our Zebrafish Retinal Vascular Disease Models

The retinal abnormalities in our hyperglycemic zebrafish model are consistent with those of diabetic retinas, showing hyaloid retinal vasodilation as well as elevated vascular endothelial growth factor (VEGF) levels, marked thinning of the inner nuclear layer and inner plexiform, and cone photoreceptor cells. The photoreceptor neuron layer is affected. Among them, we provide pdx1 mutants in zebrafish that can be used to study hyperglycemia-induced retinal angiogenesis. These zebrafish models can help you screen new drug candidates for DR treatment.

In addition, we provide von Hippel-Lindau (VHL) knockout zebrafish embryos in which severe neovascularization of choroidal and vitreous vessels, as well as retinal detachment and macular edema can be observed. The VHL mutant zebrafish model can help you study neovascular AMD. We aim to provide a well-established zebrafish model of retinal vasculopathy to help you understand developmental processes, identify potential causative genes and factors in human eye diseases, and develop new drug treatments.

Advantages

• Live Imaging of Zebrafish
• Accessibility of zebrafish genes and embryos
• High-throughput gene/drug screening
• Simple and efficient manipulation of multiple genes at a physiologically relevant level

References

1. Hong Y, Luo Y. Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery. Pharmaceuticals (Basel). 2021, 14(8):716.
2. Rezzola S, 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):1291-1296.
3. Alvarez Y, et al. Genetic determinants of hyaloid and retinal vasculature in zebrafish. BMC Dev Biol. 2007, 7:114.

For research use only. Not intended for any clinical use.