Zebrafish Glaucoma Models

Glaucoma, a heterogeneous group of diseases characterized by optic neuropathy, retinal ganglion cell shedding and visual field loss, is the second leading cause of blindness worldwide. The exact mechanism by which glaucoma occurs is unknown. Current treatments are far from satisfactory. Although traditional human genetic analysis is limited in identifying causative genes for complex diseases, mutation screening in animals can provide insights into disease etiology.

The zebrafish (Danio rerio) has become a major model animal for studying human disease because it enables powerful forward and reverse genetic analyses to rapidly identify genetic loci and study their role in disease processes. The anatomy, physiology, and genetic conservation of important ocular tissues that play a key role in maintaining intraocular pressure (IOP) in zebrafish and humans strongly suggest that zebrafish are a promising model animal for the study of glaucoma. Currently, zebrafish have been used to demonstrate that SIX6 variants disrupt neural retinal development and lead to reduced RGC numbers and increased risk of glaucoma-related visual impairment. In addition, Bugeye mutants with high intraocular pressure, enlarged eyeballs, morphological abnormalities, and functional deficits in the retina were identified as models of myopia and glaucoma. Scientists have recently established a number of zebrafish glaucoma models based on human glaucoma.

Fig.1 Identification of enlarged eye mutants with elevated intraocular pressure in zebrafish.

Our Zebrafish Glaucoma Models

The transgenic zebrafish developed by Creative Biogene can mimic human glaucoma, exhibiting multiple adult-onset phenotypes associated with glaucoma, including myopia enlargement, increased intraocular pressure, and retinal ganglion cell damage. In addition, we can assess what is happening in transgenic fish in terms of the overall structure of the eye, AL morphology, intraocular pressure changes, cell number and viability in retinal ganglion cells, and optic nerve appearance by histological, physiological, immunohistochemical, and molecular methods.

Table2. Zebrafish models of glaucoma.

Method	Injury Paradigm	Ocular Phenotype	Model
Gene-Targeted	cpamd8	Iridocorneal angle hypoplasia	Primary open angle glaucom
	cyp1b1	Neural crest migration into the anterior segment	Primary open angle glaucom
	foxc1	RGC loss	Primary open angle glaucom
	gpatch3	Anterior chamber angle hypoplasia and a decreased number of iridophores	Primary open angle glaucom
	guca1c	RGC apoptosis	Primary open angle glaucom
	ocrl	Defective cilia formation in Kupffer vesicles	Primary open angle glaucom
	pitx2	Abnormal development of the cornea, iris, and iridocorneal angle	Primary open angle glaucom
	pmel	Profound pigmentation defects and enlarged anterior segments	Pigmentary glaucoma
	six6	Smaller eyes and reduced number of RGC	Primary open angle glaucom
	Tg (Bugeye)	Decreased retinal cell densities and diminished outer retinal function	Primary open angle glaucom
	wdr36	Thinner retinal layers and smaller eyes	Primary open angle glaucom
Chemical-Induced	N-Methyl-D-aspartic acid (NMDA)	RGC loss	Glaucoma
Oxidative Stress-Induced	hydrogen peroxide	RGC injury	Glaucoma

Advantages

Simple and efficient manipulation of multiple genes at a physiologically relevant level
High-throughput gene/drug screening
Efficiently generate large lineages with modest space and time requirements

Creative Biogene aims to provide a valuable tool for studying the etiology of glaucoma and developing new drugs as an affordable high-throughput system. If you would like to learn more about zebrafish models, please feel free to contact us.

References

Veth KN, et al. Mutations in zebrafish lrp2 result in adult-onset ocular pathogenesis that models myopia and other risk factors for glaucoma. PLoS Genet. 2011, 7(2):e1001310.
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.