Extensive studies have demonstrated that adenosine receptors (ARs) may serve as neuroprotective therapeutic targets. And AR may play a role in the prevention of RGC loss in glaucoma. The use of adenosine receptor-related drugs to protect the RGC in glaucomatous eyes may be a very promising glaucoma therapy.
Although glaucoma cannot be cured, it can be managed with proper management. We hope that new developments in adrenergic modulators may lead to more options for glaucoma drug therapy. Ace Therapeutics provides resources and research to support the development of drugs with specific receptor effects and demonstrate their efficacy and safety.
Adenosine Receptors as Promising Targets for Glaucoma
Various G protein-coupled receptors are used as therapeutic targets for various diseases, and ARs are also G protein-coupled receptors that can be used as therapeutic targets for glaucoma. ARs have four isoforms that have been widely used as clinical candidates for the treatment of ocular diseases. ARs are distributed throughout the body and are also found in numerous ocular tissues such as the ciliary body, trabecular meshwork (TM), and retina. Therefore, activation or inactivation of ARs in the eye can affect aqueous humor formation and outflow as well as IOP homeostasis. In addition, ARs are also associated with optic neuron function.
Adenosine receptor agonists, a new class of drugs for glaucoma, can act through a variety of physiological processes. A number of AR selective agonists have emerged to achieve IOP-lowering effects by acting on the four known adenosine receptor subtypes A1, A2A, A2B and A3. The figure below shows the agonist derivatives that act with A1.
Fig. 1 Some AR agonist derivatives that act with A1. (Jacobson K A, et al., 2019)
Solutions of Adenosine Receptor Agonist Development for Glaucoma
We offer molecular drug development services to modulate adenosine signaling in glaucoma physiopathology, including several sub-receptor targets.
Table 1. Our specific solutions for adenosine receptor agonist for glaucoma.
| Development Strategies | Our Solutions |
|---|---|
| A1AR agonists | A1AR is widely expressed in ocular tissues. We develop selective agonist activation of A1AR to act as a neuromodulator of RGC through the Müller cell mechanism and to bind adenosine in TM to secrete the associated protein to control aqueous efflux. |
| A2AAR agonists | A2AAR is distributed in multiple locations in the retina and candidate targets for glaucoma include OPA-6566, CGS-21680, 2-O-Ado, 2-CN-Ado and ATL-313. A2AAR agonists have been shown to reduce IOP, anti-inflammatory and increase ONH blood flow. |
| A2BAR agonists | There are relatively few selective ligands available for A2BAR. Our development aims to act on the retina and exert anti-inflammatory effects. |
| A3AR agonists | A3AR is involved in a variety of different intracellular signaling pathways. We focus on exploring the specific effects of A3AR on IOP and RGC cells. |
Key Problem Solving
- To address the specific role of AR agonists in the prevention of RGC loss in glaucoma.
- To tailor specific development programs to the four subtypes of ARs.
- To investigate and validate the key pathophysiological mechanisms of drug modulation.
- To design specifically targeted drug delivery systems.
Our services are aimed at finding new pharmacological options for the treatment of glaucoma and designing new therapies based on AR agonists. For more information and quotation of our services, please contact us.
References
- Jacobson K A, et al. Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development. Frontiers in Cellular Neuroscience, 2019, 13.
- Spinozzi E, et al. Adenosine receptors as promising targets for the management of ocular diseases. Med Chem Res, 2021, 30, 353–370.