Transgenic zebrafish mimic can human glaucoma, and are a valuable tool for further research into glaucoma etiology and drug development. Ace Therapeutics is an expert in zebrafish ocular disease research and has successfully developed zebrafish glaucoma genetic models. These models simulate human primary open-angle glaucoma (POAG) and pigmentary glaucoma. Our goal is to help you capture the milestone data needed to make critical decisions in the early stages of drug discovery.
Glaucoma, the second leading cause of blindness worldwide, is characterized by progressive and irreversible visual field loss and severe visual impairment secondary to RGC loss. Glaucoma's specific mechanism is still unclear. There is an urgent need to understand glaucoma physiopathology at the cellular and molecular levels and develop potential therapies to prevent and treat this severe blinding disease. The zebrafish is an ideal model animal for eye disease research, mainly due to its ability to perform forward and reverse genetic analysis, allowing the rapid identification of genetic loci and the study of their role in disease processes. Importantly, the anatomy, physiology, and genetics of zebrafish eye tissue play a key role in maintaining intraocular pressure (IOP) in both zebrafish and humans, suggesting that the zebrafish is a promising animal model to study glaucoma.
Fig. 1. Adult bugeye zebrafish have enlarged eye globes, thinned retinas, and elevated intraocular pressure without iridocorneal angle obstruction or malformation. (Veth KN, et al., 2011)
Adult zebrafish and mammals have similar intraocular pressure (IOP) distributions that closely mimic human glaucoma disease risk phenotypes. Since the establishment of our advanced zebrafish model platform, Ace Therapeutics has been committed to understanding mutated genes related to human glaucoma. This has enabled us to construct a highly reproducible, easy-to-operate, and robust transgenic zebrafish glaucoma model. This model exhibits many pathogenic phenotypes associated with human glaucoma, including chronically elevated IOP, enlarged eyes, and retinal ganglion cell death with progressive optic nerve damage.
In order to accurately characterize the biological function of the zebrafish model and verify the efficacy of candidate compounds in reducing glaucoma progression in the zebrafish model, our researchers have developed the following endpoint evaluation services, including but not limited to:
Ace Therapeutics has successfully developed various genetic models of zebrafish glaucoma. Our researchers modify the expression of single/multiple genes using gene editing tools to generate zebrafish glaucoma models with specific genetic mutations. These models help you study from causal genes to cell and tissue levels, providing pathological information on glaucoma from embryonic development to adulthood.
Ace Therapeutics offers the following genetic zebrafish models, including but not limited to:
Tab.1. Ace Therapeutics' zebrafish models for congenital cataract.
Gene | Ocular Phenotype | Model |
---|---|---|
cpamd8 | Iridocorneal angle hypoplasia. | POAG |
cyp1b1 | Neural crest migration into the anterior segment. | POAG |
foxc1 | RGC loss. | POAG |
gpatch3 | Anterior chamber angle hypoplasia and a decreased number of iridophores. | POAG |
guca1c | RGC apoptosis. | POAG |
ocrl | Defective cilia formation in Kupffer vesicles | POAG |
pitx2 | Abnormal development of the cornea, iris, and iridocorneal angle. | POAG |
pmel | Profound pigmentation defects and enlarged anterior segments. | Pigmentary glaucoma |
six6 | Smaller eyes and reduced number of RGC. | POAG |
Tg (Bugeye) | Decreased retinal cell densities and diminished outer retinal function. | POAG |
wdr36 | Thinner retinal layers and smaller eyes. | POAG |
To attract our customers, our researchers have also developed chemically induced (zebrafish model of NMDA-induced retinal neurodegeneration) and oxidative stress-induced (zebrafish model of hydrogen peroxide-induced retinal damage) glaucoma models. Please consult our scientists for more detailed information.
Ace Therapeutics aims to provide a powerful analytical tool for global clients' glaucoma program development. 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