Glaucoma affects the lives of tens of millions of people worldwide, causing irreversible blindness. And the number of people affected is expected to continue to grow. Therefore, there is a significant unmet need for therapies that can improve current glaucoma treatments.
Ace Therapeutics focuses on emerging approaches to glaucoma treatment, including nucleic acid-based gene therapy. siRNA can be used to inhibit the expression of specific genes, thus providing a highly promising outcome for the treatment of ocular diseases, including glaucoma. Based on this, we utilize siRNA-based gene silencing strategies to treat glaucoma, providing researchers with development services to study the composition and mechanisms of siRNA drugs, offering solutions to the fundamental challenges faced during development.
siRNA-based Strategy for Glaucoma Development
siRNA is a double-stranded RNA molecule that regulates gene expression by targeting mRNA degradation leading to gene silencing. In glaucoma treatment, siRNA can be used to silence the expression of harmful genes. Reducing IOP is a major approach to reduce glaucoma progression. The siRNA-based glaucoma therapies that have been explored, such as targeting the epinephrine receptor, which controls atrial fluid to lower IOP, can significantly reduce long-term IOP and are achieved by topical administration.
Fig. 1 Glaucoma therapies based on siRNA to reduce atrial inflow or increase atrial flow to lower IOP. (Guzman-Aranguez A, et al., 2013)
siRNA-based Solutions for Glaucoma Development
We customize siRNA-based gene therapy strategies for glaucoma, providing different therapeutic targets currently under development or with potential and developing siRNA drugs for glaucoma treatment.
Table 1. Our specific solutions for siRNA-based gene therapy for glaucoma.
| Target | Effect | Treatment |
|---|---|---|
| Na-K-ATPase | Create an ionic gradient in the ciliary epithelium that contributes to aqueous humor production. | siRNA against this target can reduce IOP by reducing aqueous humor production. |
| Purine receptor P2Y2 | Levels of this receptor agonist are elevated in patients with glaucoma, leading to an increase in IOP. | siRNA targeting the P2Y2 receptor significantly reduced IOP. |
| Cochlin | It acts as a mechanical sensor to detect fluid shear changes in the ECM, which responds to changes causing multimerization that can impede water flow out and increase IOP. | Cochlin silencing by siRNA lowers IOP. |
| Mutated myocilin | Mutated myocilin accumulation induces TM apoptosis, followed by TM blockage and increased resistance to atrial water outflow. | Design of siRNA precursors to inhibit mutant myocilin proteins in TM cells. |
| Caspase-2 | Proteins associated with the initiation or execution of programmed cell death in the RGC. | siRNA targeting caspase-2 has neuroprotective effects and protects RGC. |
| RhoA | Regulate the contraction of TM actin stress fibers. | The RhoA siRNA leads to a significant decrease in mRNA and protein expression of RhoA and reduces IOP. |
| Smad7 | Regulate ECM deposits in TM. | Downregulation of Smad7 by siRNA interrupts the expression of several ECM components by TGF-β2 in human TM cells. |
| CTGF | Affect ECM protein synthesis in TM cells. | siRNA attenuates CTGF expression to prevent TGF-β2-induced fibronectin accumulation and improve atrial efflux in TM. |
Specific Service Items
- Design siRNAs for targeting and repressing target genes, chemically synthesize double-stranded oligonucleotides
- Validate effective inhibition of target expression in cell cultures
- Preclinical animal testing
- Develop delivery systems
- More specific services
The use of gene silencing for the treatment of glaucoma holds promise. If you have a target of interest or a siRNA drug under investigation, you can contact us for available experience and resources to address important questions in your research.
References
- Guzman-Aranguez A, et al. Small-interfering RNAs (siRNAs) as a promising tool for ocular therapy. Br J Pharmacol, 2013, 170(4):730-47.
- Daliri K, et al. Glaucoma, Stem Cells, and Gene Therapy: Where Are We Now? IJSC, 2017, 10:119-128.