Zebrafish Eye Defect Models

Failure to close the optic fissure is a cause of ocular defects characterized by the persistent presence of fissures that may span the iris, ciliary body, zonules, retina, choroid, and optic nerve. Eye defects have been reported in up to 11.2% of blind children worldwide, with an estimated incidence of 0.5-7.5 per 10 000 births, and are often associated with other congenital ocular abnormalities.

The zebrafish eye defect model provides an important paradigm for understanding optic fissure morphogenesis, and mutations in orthologs of zebrafish human eye defect causative genes lead to a range of observed retinal and lens defects. Zebrafish corneas are very similar to human corneas in both morphology and gene expression. For example, homozygous pax6b mutants share striking phenotypic similarity with human patients heterozygous for PAX6 mutations, showing anterior chamber hypoplasia, including reduced anterior chamber volume, lens defects, and incomplete separation of the cornea and lens. In addition to these morphological phenotypes, homozygous pax6b mutants are also characterized by reduced gene expression in the epithelium and ectopic expression of genes in the corneal endothelium.

Fig.1 pax6b mutants (also named sunrise) present an abnormal anterior chamber with severe corneal endothelium defects.

Our Zebrafish Eye Defect Models

To date, most of the genes associated with eye deformities cause defects when disrupted alone, but in many cases mutations in individual genes may not show any defects unless combined with other genetic mutations or environmental risk factors. Therefore, Creative Biogene is working to identify these genetic interactions and the complex networks in which they are involved in zebrafish through genome editing technology.

Our zebrafish mutants homozygous for the pax2a mutation exhibit defects in optic fissure closure, lack the midbrain, midbrain-hindbrain boundary, and cerebellum, fail to feed and die within 2 weeks. Additionally, we can perform differential screening of the corneal transcriptome versus the skin (dermis, epidermis) transcriptome. Our Gene Ontology analysis in zebrafish will help your understanding of the molecular mechanisms of different human corneal diseases. Furthermore, our mutant zebrafish will represent a promising model for screening drugs that inhibit the development of Peters abnormality and other anterior chamber agenesis phenotypes.

Advantages

• Genetic screening of mutants for embryonic development
• Efficiently perform positional cloning
• Ease of loss-of-function genetic analysis
• Real-time observation of disease progression

References

1. Cavodeassi F, Wilson SW. Looking to the future of zebrafish as a model to understand the genetic basis of eye disease. Hum Genet. 2019, 138(8-9):993-1000.
2. Takamiya M, et al. Molecular description of eye defects in the zebrafish Pax6b mutant, sunrise, reveals a Pax6b-dependent genetic network in the developing anterior chamber. PLoS One. 2015, 10(2): e0117645.
3. Richardson R, et al. The zebrafish eye-a paradigm for investigating human ocular genetics. Eye (Lond). 2017, 31(1):68-86.
4. Gestri G, Link BA, Neuhauss SC. The visual system of zebrafish and its use to model human ocular diseases. Dev Neurobiol. 2012, 72(3):302-27.

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