- Zebrafish Germ Cell Tumor Models
- Zebrafish Intestinal Cancer Models
- Zebrafish Intrahepatic Cholangiocarcinoma Models
- Zebrafish Liver Cancer Models
- Zebrafish Melanoma Models
- Zebrafish Neurofibromatosis Type 1 Models
- Zebrafish Pancreatic Cancer Models
- Zebrafish Retinoblastoma Models
- Zebrafish Rhabdomyosarcoma Models
- Zebrafish Thyroid Cancer Models
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.
