Glaucoma is uniformly characterized by retinal ganglion cell (RGC) death. However, the disease is also clinically divided into different types. For each type of glaucoma, a single animal model of high intraocular pressure (IOP) may not accurately simulate the different glaucoma forms. Compared to experimentally induced glaucoma models, genetic glaucoma animal models are able to more precisely control molecular pathways to simulate different types of glaucoma.
Therefore, Ace Therapeutics provides advanced cell biology and powerful genetic tools for use in laboratory mice and is dedicated to constructing many new mouse models of glaucoma, providing important insights for glaucoma research.
Glaucoma-Related Phenotypes that Can Be Modeled in Mice
Mice are a powerful tool to unravel the genetic causes, susceptibility factors and physiological pathways behind glaucoma in humans. First, there are similarities between human and mouse eyes. Second, a combination of advanced cell biology and genetic tools can be used in mice. These enable the mouse to be an excellent system for studying the molecular pathways underlying the pathophysiology of glaucoma.
Fig. 1 Glaucoma-related phenotypes that can be modeled and studied in mice. (Fernandes K A, et al., 2015)
In glaucoma, a variety of different pathological damages can be observed in different ocular tissues. However, trying to study this through human genetics is difficult, so scientists use standard mouse genetic tools to identify new genes and pathways that affect glaucoma. Commonly used mouse genetic models, such as high IOP mice, include DBA/2J mice, myocilin mutant mice and other genetic models.
Our Services
As glaucoma research continues to evolve, we are committed to integrating more information from glaucoma research into mouse models to improve the ability of mice to study the pathophysiology of glaucoma.
Table 1 Some common mouse models of glaucoma that we were able to construct.
| Category | Genetic Mouse Model | Overview |
|---|---|---|
| Ocular hypertensive models | DBA/2J mice | Mutations in Gpnmb and Tyrp1 result in elevated IOP and RGC loss and are used to study the genetics of high IOP. |
| Myocilin mutant mice | Mutations in the myocilin gene (MYOC) cause high IOP and glaucoma. We can manipulate the levels of the MYOC gene in mice and test for glaucoma-specific alleles in mice to better understand the normal and pathological functions of myocilin. | |
| Mutant Prss56 mice | For studying phenotypes associated with primary angle-closure glaucoma. | |
| Glaucoma-relevant RGC death models | DBA/2J mice | DBA/2J mice have been used to study many cell biological problems associated with high IOP-induced optic nerve degeneration and RGC death. |
| E50Ktg transgenic mice | For understanding the molecular mechanism of RGC death in normal tension glaucoma. | |
| Wdr36 mutant mice | Wdr36 may be the cause of glaucoma and is a predisposing factor for the development of glaucoma. This mouse model can be used to assess the tissue-specific function of Wdr36 in the pathogenesis of glaucoma. | |
| GLAST or EAAC1 deficient mice | Mice with GLAST or EAAC1 exhibit a different time course of RGC degeneration that can be used to determine if it is associated with RGC loss in human normal tension glaucoma. | |
| Developmental glaucoma models | Transcription factor (PITX2, FOXC1, FOXF2, LMX1B, PAX6) mutant mice | Mice carrying various signaling mutations can be used to understand the inducing events that drive glaucomatous anterior segment development. |
We provide research services that primarily include opening up research avenues to construct new genetic mouse models.
- Genomic studies. We identify genes and loci associated with glaucoma through genomic studies, including GWAS, NGS and other analyses.
- Genome editing. We construct genetically engineered mice using CRISPRs technology, enabling rapid creation in a matter of months, as well as integration of larger DNA fragments into the mouse genome, generating conditional alleles to study the broad function of genes.
Applications
- For testing and evaluation of improved glaucoma therapies
- For exploring the complex physiological interactions in glaucoma
- For studying the cell biology of glaucoma-related phenotypes
Reference
- Fernandes K A, et al. Using genetic mouse models to gain insight into glaucoma: past results and future possibilities. Experimental eye research, 2015, 141: 42-56.