Zebrafish Ocular Disease Models

Visual impairment is a major health problem affecting millions of people around the world. Major causes of visual impairment and blindness include cataract, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR), with cataracts being the leading cause of blindness worldwide. Strategies to develop animal models that closely mirror human ocular diseases are necessary for a better understanding of the underlying causes and simultaneously for the development of novel therapeutic approaches. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programs.

Modelling Human Eye Disease in the Zebrafish

The eyes of the zebrafish are large relative to the overall size of the zebrafish, making eye bud manipulation feasible during early embryogenesis. Zebrafish are visually responsive by 72 h post fertilization (h.p.f.) by which time the retina resembles adult retinal morphology that is functionally and anatomically similar to humans. Contrary to mice that have a rod-dominated vision, zebrafish have a cone-dominant vision like humans, which is a precondition to study human disorders associated with cone degeneration, such as AMD. The eyes of zebrafish develop fast from 12 hpf and display a functional visual system by 5 dpf. This is significantly faster compared with mice and allows to us study visual function already in 5-day-old larvae. Moreover, a large amount of genetic information available from zebrafish mutants associated with defective visual development and function illustrates the power of this model for understanding human ophthalmological disorders.

Figure 1. Cross-sectional histology of the human and zebrafish retina. (Richardson R, et al. 2017)

Our Zebrafish Ocular Disease Models

Over the past two decades, extensive collections of zebrafish lines carrying mutations in genes involved in early embryonic development have been generated—some of these mutations in genes important for eye formation and associated with eye malformations in humans. Besides, many transgenic lines have been generated at Creative Biogene to enable the close monitoring of organogenesis and the manipulation of gene activity in a tissue-directed way. We mainly use the three approaches to abrogate gene function in zebrafish: stable lines carrying mutations (mutants); morpholino-based knock-down of gene function; and use of CRISPR/Cas9 gene editing to disrupt gene function in injected embryos. Many human pathological conditions from Alzheimer's disease to metabolic syndrome have been successfully modelled in zebrafish. Our zebrafish ocular disease models include but not limited to:

Zebrafish cataracts models
Zebrafish glaucoma models
Zebrafish age-related macular degeneration (AMD) models
Zebrafish diabetic retinopathy (DR) models
Zebrafish ocular coloboma models
Zebrafish microphthalmia/anophthalmia models
Zebrafish corneal dystrophies models
Zebrafish aniridia models
Zebrafish choroideremia models
Zebrafish leber congenital amaurosis models

With extensive experience in zebrafish research, our scientists can help you choose the right model and experimental design to achieve your research and development goals.

References

Chhetri J, et al. Zebrafish—on the move towards ophthalmological research. Eye, 2014, 28(4): 367-380.
Cavodeassi F, Wilson S W. Looking to the future of zebrafish as a model to understand the genetic basis of eye disease. Human genetics, 2019: 1-8.
Richardson R, et al. The zebrafish eye—a paradigm for investigating human ocular genetics. Eye, 2017, 31(1): 68-86.

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

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