Targeting the A3 adenosine receptor for glaucoma treatment (review)

Abstract

Glaucoma is a worldwide disease and the second leading cause of blindness. Current treatments are associated with a number of side-effects and poor compliance, due to the requirement for treatment administration several times a day. These treatments typically aim to lower intraocular pressure (IOP); however, they are unable to protect retinal ganglion cells (RGCs) from undergoing apoptosis, which is the main cause of vision loss. A3 adenosine receptor (A3AR) agonists have been found to protect normal cells from undergoing apoptosis via the downregulation of death signals. Furthermore, A3AR agonists have been reported to have several ophthalmological effects, including the prevention of ganglion cell apoptosis in vitro and in vivo and anti‑inflammatory effects in experimental models of autoimmune uveitis. CF101, an orally bioavailable A3AR agonist, has been analyzed in dry eye syndrome phase II clinical trials and was identified to be safe and well tolerated. The anti‑inflammatory effect of CF101 was shown to significantly improve corneal staining, tear meniscus and tear break‑up time in dry eye patients. In addition, CF101 was found to decrease IOP in patients. The safety and efficacy of CF101, together with its suitability for oral administration, indicates that it has potential as a candidate drug for the treatment of glaucoma.