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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 treatments available 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 effective treatments are needed, such as those targeting the neuroprotection of RGCs. Adenosine A3 receptor (A3R) activation confers protection to RGCs following an excitotoxic stimulus. In this work, we investigated whether the activation of A3R could also afford protection to RGCs in the laser-induced ocular hypertension (OHT) model, a well-characterized animal model of glaucoma. The intravitreal injection of 2-Cl-IB-MECA, a selective A3R agonist, abolished the alterations induced 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 A3R agonist promoted the survival of RGCs, attenuated the impairment in retrograde axonal transport, and improved the structure of the optic nerve. Taking into consideration the beneficial effects afforded by 2-Cl-IB-MECA, we can envisage that A3R activation can be considered a good therapeutic strategy to protect RGCs from glaucomatous damage.

SUBMITTER: Boia R 

PROVIDER: S-EPMC7253479 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Activation of adenosine A<sub>3</sub> receptor protects retinal ganglion cells from degeneration induced by ocular hypertension.

Boia Raquel R   Salinas-Navarro Manuel M   Gallego-Ortega Alejandro A   Galindo-Romero Caridad C   Aires Inês D ID   Agudo-Barriuso Marta M   Ambrósio António Francisco AF   Vidal-Sanz Manuel M   Santiago Ana Raquel AR  

Cell death & disease 20200527 5


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 treatments available 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 effective treatments are needed, such as those  ...[more]

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