Customized In Vivo Ocular Models ace

Customized Zebrafish Models of Cataract

The zebrafish is a useful model for congenital cataracts because it has lens proteins very similar to humans. As an expert in zebrafish ocular disease research, Ace Therapeutics has successfully developed dozens of drug-validated zebrafish gene mutation cataract models. This helps our global customers discover the pathogenesis of human cataracts and test the potential anti-cataract efficacy of candidate compounds. Our goal is to help you capture the milestone data you need to make critical decisions in the early stages of drug discovery.

Zebrafish Models of Cataract

Advantages of Zebrafish in Studying Cataract Disease

A cataract is an eye disease characterized by clouding of the lens, including congenital cataracts and age-related cataracts, and is currently the leading cause of human blindness worldwide. The mechanism by which this occurs is related to proteins aggregating due to various post-translational modifications. Genetic studies have identified a variety of causal mutations in congenital or other early-onset cataracts. However, the causal genes for many cataract cases remain unidentified. Therefore, promising animal models are urgently needed to reveal cataract pathogenesis and thus discover effective preventive measures. Compared with rodents, zebrafish have 82% identical homologous genes with human disease-related genes, and can use gene editing tools to induce multiple gene mutation models, potentially screening thousands of candidate compounds with human cataract disease therapeutic potential.

Fig. 1. Overview of the main steps of the cataract gene evaluation pipeline. (Zhao D, et al., 2021)

Service Overview

Zebrafish is a powerful model for lens biology. Their transparent outer embryos not only facilitate lens experiments but also make it relatively easy to express introduced proteins and explore their effects on lens function. In recent years, Ace Therapeutics ophthalmology experts have had access to genetic and physical tools to develop a zebrafish cataract model. In addition, we also provide in vivo pharmacology studies in zebrafish models mimicking human ocular diseases.

Explore Ace Therapeutics' Zebrafish Models of Cataract

Our zebrafish cataract models are mainly congenital cataract models formed by knocking out pathogenic genes related to human cataracts in zebrafish embryos to induce cataracts or other lens abnormalities. In the provided zebrafish cataract model, mutations in crystallins predominate, followed by mutations in various growth or transcription factors, connexins, membrane proteins, and lipid metabolism.

Ace Therapeutics provides congenital cataract models caused by the following gene mutations, including but not limited to:

Tab.1. Ace Therapeutics' zebrafish models for congenital cataract.

Gene	Ocular Phenotype
CRYAA(αA-crystallin)	crystal-like opacity sporadically spreading across the lens, or frequent droplets covering a large fraction of the lens.
CRYAB(αB-crystallin)	same as CRYAA.
CRYGC(γC-crystalline)	same as CRYAA.
CRYGD(γD-crystallin)	same as CRYAA.
DNase1l1l	retaining nuclei in lens fiber cells.
epha2	smaller eye, lens opacification and coloboma.
mab21l2	microphthalmia, colobomas, small and disorganized lenses, cornea dysgenesis.
plod3	distorted and dislocated lenses from an early stage dislocated, lack of normal lens capsule.
rbm24	coarse and irregular lens, small-size retina and lens.
aqp0a	nuclear opacity and widespread cortical fiber-to-fiber membrane stacking defects.
gja8	various sizes of lens opacity.
kpna4	rugged and cloudy center part of the lens.
pgrmc1	minor or mild nuclear central mass with fiber cell disorganization, and moderate or severe nuclear density with pitting.
aqp0a	nuclear opacity and widespread cortical fiber-to-fiber membrane stacking defects.
gja8	various sizes of lens opacity.
kpna4	rugged and cloudy center part of the lens.
pgrmc1	minor or mild nuclear central mass with fiber cell disorganization, and moderate or severe nuclear density with pitting.

In addition to the above, Ace Therapeutics also provides a zebrafish cataract model formed by physical stimulation. Our researchers induce cataracts by irradiating zebrafish lenses with 254 nm UV-C for 7 days.

Advantages of Ace Therapeutics' Zebrafish Models of Cataract

Supporting high-throughput drug screening.
Provide polygenic manipulation at the physiological level.
Lens opacity analysis (in vivo zebrafish imaging).
Accessibility to zebrafish genes and embryos.
Providing supplementary in vivo pharmacology studies.
Custom models for polygenic mutations.

Ace Therapeutics is committed to providing powerful analysis tools for human cataract disease research. Importantly, our expert team can also develop a customized cataract model by knocking out a specific gene according to your needs. 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

Zhao D, Jones JL, Gasperini RJ, et al. Rapid and efficient cataract gene evaluation in F0 zebrafish using CRISPR-Cas9 ribonucleoprotein complexes. Methods. 2021, 194:37-47.
Hong Y, Luo Y. Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery. Pharmaceuticals (Basel). 2021, 14(8):716.

For Research Use Only.

Get in Touch