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Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure.

ABSTRACT: Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness, characterized by optic nerve damage and retinal ganglion cell (RGC) death. Elevated intraocular pressure (IOP) is a main risk factor of glaucoma. Neuroinflammation plays an important role in glaucoma. We have been demonstrating that elevated pressure triggers microglia reactivity that contribute to the loss of RGCs. Adenosine, acting on adenosine receptors, is a crucial modulator of microglia phenotype. Microglia express all adenosine receptors. Previously, we demonstrated that the activation of adenosine A3 receptor (A3R) affords protection to the retina, including RGCs, unveiling the possibility for a new strategy for glaucoma treatment. Since microglial cells express A3R, we now studied the ability of a selective A3R agonist (2-Cl-IB-MECA) in controlling microglia reactivity induced by elevated hydrostatic pressure (EHP), used to mimic elevated IOP. The activation of A3R reduced EHP-induced inducible nitric oxide synthase (iNOS) expression, microglia migration and phagocytosis in BV-2 cells. In retinal microglia, proliferation and phagocytosis elicited by EHP were also decreased by A3R activation. This work demonstrates that 2-Cl-IB-MECA, the selective agonist of A3R, is able to hinder microglia reactivity, suggesting that A3R agonists could afford protection against glaucomatous degeneration through the control of neuroinflammation.

SUBMITTER: Ferreira-Silva J

PROVIDER: S-EPMC7582754 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure.

Ferreira-Silva Joana J Aires Inês D ID Boia Raquel R Ambrósio António Francisco AF Santiago Ana Raquel AR

International journal of molecular sciences 20200930 19

Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness, characterized by optic nerve damage and retinal ganglion cell (RGC) death. Elevated intraocular pressure (IOP) is a main risk factor of glaucoma. Neuroinflammation plays an important role in glaucoma. We have been demonstrating that elevated pressure triggers microglia reactivity that contribute to the loss of RGCs. Adenosine, acting on adenosine receptors, is a crucial modulator ...[more]

PMID: 33007835

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Dataset Information

Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure.

Publications

Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure.

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