Zebrafish Cataract Models

Cataract is a cloudy development that interferes with the transmission of light to the retina, mainly including congenital cataracts and age-related cataracts (ARC), which are currently one of the leading causes of human blindness worldwide. Promising animal models are urgently needed so that a better understanding of the mechanisms that lead to cataracts in the lens can lead to the development of preventive strategies. The zebrafish has a more distant phylogeny from humans than rodents, but it shares 82% of orthologs of human disease-related genes. Furthermore, zebrafish have a short generation time of only 2-4 months, a single mating pair produces approximately 200 offspring per week, and is easy to maintain at low cost. Importantly, transparent zebrafish embryos develop in utero, enabling visualization of early organogenesis.

In recent years, the zebrafish has become a powerful model for examining the biology of the ocular lens. Not only do their transparent outer embryos facilitate lens experiments, but it is also relatively easy to express introduced proteins and explore their effects on lens function. Multiple studies have shown that lens development and protein content are well preserved between zebrafish and mammals, allowing zebrafish research to translate to our understanding of lens disease in humans. In addition, zebrafish are widely used in ocular drug discovery, such as screening new anti-angiogenic compounds or neuroprotective drugs, and ocular toxicity testing.

Fig.1 Cross-sectional views of human and zebrafish retinas showing similar structural features of retinal layers.

Our Zebrafish Cataract Models

Our zebrafish cataract model is mainly congenital cataract. Among the known cataract-causing genetic mutations, mutations in lens crystallins account for the majority, followed by mutations in various growth or transcription factors, connexins, membrane proteins, and lipid metabolism. We can provide zebrafish models of congenital cataracts with multiple genetic mutations for studying lens crystallin aggregation and cataract prevention.

Tabel.1 Genetic mutations of zebrafish models for congenital cataract.

Function	Mutant Gene	Ocular Phenotype
encoding crystallins	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
encoding developmental factors	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
encoding membrane proteins	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

Advantages

Live Imaging of Zebrafish
Accessibility of zebrafish genes and embryos
High-throughput gene/drug screening
Simple and efficient manipulation of multiple genes at a physiologically relevant level

Creative Biogene is committed to providing you with excellent tools to study the mechanism of crystal participation in ARC, helping you to uncover the specific mechanism of cataract formation. If you would like to learn more about zebrafish models, please feel free to contact us.

References

Posner M, et al. Why does the zebrafish cloche mutant develop lens cataract? PLoS One. 2019, 14(3): e0211399.
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. Not intended for any clinical use.

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