Activation of adenosine A3 receptor protects retinal ganglion cells from degeneration induced by ocular hypertension

Abstract

Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness.This disease is characterized by optic nerve damage and retinal ganglion cell (RGC) death. The current treatmentsavailable target the lowering of intraocular pressure (IOP), the main risk factor for disease onset and development.However, in some patients, vision loss progresses despite successful IOP control, indicating that new and effectivetreatments are needed, such as those targeting the neuroprotection of RGCs. Adenosine A3receptor (A3R) activationconfers protection to RGCs following an excitotoxic stimulus. In this work, we investigated whether the activation ofA3R could also afford protection to RGCs in the laser-induced ocular hypertension (OHT) model, a well-characterizedanimal model of glaucoma. The intravitreal injection of 2-Cl-IB-MECA, a selective A3R agonist, abolished the alterationsinduced by OHT in the negative and positive components of scotopic threshold response (STR) without changing a-and b-wave amplitudes both in scotopic and photopic conditions. Moreover, the treatment of OHT eyes with the A3Ragonist promoted the survival of RGCs, attenuated the impairment in retrograde axonal transport, and improved thestructure of the optic nerve. Taking into consideration the beneficial effects afforded by 2-Cl-IB-MECA, we can envisagethat A3R activation can be considered a good therapeutic strategy to protect RGCs from glaucomatous damage.