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Customized Zebrafish Models of Corneal Dystrophy

Zebrafish are widely used to study the function of genes mutated to cause corneal dystrophy due to their genetic accessibility. Ace Therapeutics has established a high-quality model of corneal dystrophy in a genetically tractable organism (zebrafish) and validated it extensively. These models provide an opportunity to explore vision loss due to corneal dystrophy, which is helpful for our clients to gain insight into the pathogenesis of the disease.

Zebrafish Models of Corneal Dystrophy

What Are Corneal Dystrophies?

Corneal dystrophies are a group of rare, inherited, progressive eye disorders that cause changes in the cornea that cause vision disturbances, including blurred vision, glare, and vision loss (decreased vision) without inflammation, infection, or other eye disease. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes, and little is known about the cornea and the genetic mechanisms underlying its differentiation. Animal models can be used to further characterize the gene signaling network of corneal dystrophy and improve therapeutic strategies. Zebrafish cornea anatomy is similar to vertebrates. It lacks vasculature, is highly innervated, and consists of three cell layers: corneal epithelium, stroma, and endothelium. This overall structure is already evident at 5 to 7 dpf. Beyond that, zebrafish corneas are very similar to human corneas in gene expression. Therefore, the transgenic zebrafish corneal dystrophy model will be a promising model to understand corneal differentiation mechanisms and to screen drugs for the corneal dysplasia phenotype.

Fig. 1. Comparison of the human and zebrafish eye. Fig. 1. Comparison of gene expression in the cornea of wild type zebrafish at 7 dpf (A-O) and 1-month stage (A-O). (Takamiya M, et al., 2015)

Service Overview

Due to the thinner stroma and presence of rodlet cells in the zebrafish cornea, zebrafish are seldom utilized to study normal or pathological human corneas. However, they are often used to study genetic corneal dystrophies caused by specific mutations. Ace Therapeutics is always on the way to exploring genetic corneal disorders. Benefiting from a deep and comprehensive knowledge of human zebrafish and horsefish genes and a deep understanding of inherited corneal dystrophies, our talented scientists have developed several transgenic zebrafish corneal dystrophy models.

In order to characterize the structure and function of the wild-type zebrafish cornea, and to determine whether zebrafish orthologous gene mutations related to human corneal disease-related genes can reproduce similar disease phenotypes. Our researchers address this challenge through the following strategies, including but not limited to:

Confocal microscopy analysis
Immunohistochemistry
Central corneal thickness analysis (optical coherence tomography (OCT))
Analysis of corneal edema and endothelial cell morphology changes
Genotype analysis

Explore Ace Therapeutics' Zebrafish Models of Corneal Dystrophy

Ace Therapeutics provides our global customers with a series of transgenic zebrafish corneal dystrophy models through gene editing tools, such as focal corneal dysplasia by knocking out the lama1 gene in zebrafish. Alternatively, insertion of the BIGH3 gene containing a human dominant mutation into the zebrafish genome produces corneal abnormalities associated with human dystrophy.

We are proud that these transgenic zebrafish models of corneal dystrophy have been extensively validated, providing a testing opportunity for our customers to screen candidate compounds for alleviating corneal defects. In addition, it also provides a strong research basis for discovering the underlying genetic mechanism of corneal development and exploring the causes of corneal diseases.

Ace Therapeutics aims to provide a powerful analytical tool to help our global customers understand the mechanisms that corneal differentiation and maintain its structure and function, thereby exploring potential new therapies. 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

Hong Y, Luo Y. Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery. Pharmaceuticals (Basel). 2021, 14(8):716.
Takamiya M, Weger BD, Schindler S, 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.

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