At Ace Therapeutics, we recognize the critical need for robust preclinical models to dissect the complex role of Optineurin in glaucoma. We empower our clients to advance their understanding of glaucoma by providing custom Optn mutant mouse models.
Unraveling the Role of Optineurin in Glaucoma
Glaucoma, a primary cause of irreversible blindness, is often linked to elevated intraocular pressure (IOP). Notably, normal-tension glaucoma (NTG) occurs despite normal IOP, highlighting IOP-independent mechanisms where genetic factors play a crucial role in NTG. Optineurin is a multifunctional protein involved in critical cellular processes such as autophagy, vesicle trafficking, and NF-κB signaling. Mutations in Optn, such as the E50K and M98K variants, have been strongly associated with an increased risk of developing glaucoma. Understanding how these mutations cause retinal ganglion cell (RGC) dysfunction and death is critical for developing targeted therapeutics.
Fig. 1 Effects of the OPTN-E50K point mutation on visual function and IOP in vivo. (Zhang S Q, et al., 2021)
Explore Our Custom Optn Mutant Mouse Models
Ace Therapeutics empowers researchers and pharmaceutical companies with custom Optn mutant mouse models to study glaucoma pathogenesis, validate genetic mechanisms, and screen drug candidates.
Optn Transgenic Mice
We can construct transgenic mice that overexpress either wild-type or specific mutant forms of the human OPTN gene or mouse Optn gene, allowing for tissue-specific or global expression. For instance, our OPTN (E50K) transgenic mice overexpress the mutant Optineurin, exhibiting progressive RGC loss and optic nerve degeneration.
Optn Knock-In Mice
Using gene editing technology, our experts can construct knock-in mouse models where the endogenous mouse Optn gene is precisely mutated to carry specific glaucoma-associated variants, such as E50K or M98K. These mice exhibit normal IOP, thinner retinal layers, and reduced RGC density.
Optn Knockout Mice
We can also develop knockout mice to achieve conditional deletion of the Optn gene in specific tissues, such as the retina. Optn knockout mice are invaluable for understanding the consequences of Optineurin loss of function in glaucoma pathogenesis.
Comprehensive Evaluation Services for Optn Mutant Mouse Models
We provide in vivo and ex vivo evaluation services for Optn mutant mouse models to assess disease-relevant phenotypes, supporting our clients in investigating Optineurin-related mechanisms and evaluating potential therapeutics.
Visual Function Assessment
- Flash visual evoked potentials (f-VEP): Measures the electrical activity of the visual cortex in response to light stimuli.
- Optokinetic response (OKR): Evaluates visual acuity and tracking ability.
Retinal Structure Analysis
- Optical coherence tomography (OCT): Assess retinal thickness and layer-specific changes.
- Histological analysis: Paraffin sectioning and H&E staining to visualize retinal architecture.
Protein Enrichment and Pathway Analysis
We provide proteomic services, including protein enrichment analysis and pathway profiling, to identify specific biological processes and molecular pathways affected by Optn mutations in the retina.
Ace Therapeutics is committed to supporting glaucoma research by providing reliable animal models and robust preclinical services. Our Optn mutant mouse models serve as invaluable tools for elucidating the intricate role of Optineurin in glaucoma pathogenesis. Contact us to learn more about how our tailored solutions can empower your glaucoma research and drug development.
Reference
- Zhang S Q, et al. The E50K optineurin mutation impacts autophagy-mediated degradation of TDP-43 and leads to RGC apoptosis in vivo and in vitro. Cell Death Discov, 2021, 7(1): 49.