Abstract
Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. 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 programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future.
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Acknowledgements
We gratefully acknowledge funding from Fight for Sight UK, Moorfields Eye Charity, the Choroideremia Research Foundation, the Academy of Medical Sciences and the NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology. Thanks to Philip Luthert for providing the human retinal histology section and to Adam Dubis for his guidance with OCT imaging.
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Richardson, R., Tracey-White, D., Webster, A. et al. The zebrafish eye—a paradigm for investigating human ocular genetics. Eye 31, 68–86 (2017). https://doi.org/10.1038/eye.2016.198
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DOI: https://doi.org/10.1038/eye.2016.198
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