Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure
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...
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7218 |
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| author | Joana Ferreira-Silva Inês D. Aires Raquel Boia António Francisco Ambrósio Ana Raquel Santiago |
| author_facet | Joana Ferreira-Silva Inês D. Aires Raquel Boia António Francisco Ambrósio Ana Raquel Santiago |
| author_sort | Joana Ferreira-Silva |
| collection | DOAJ |
| description | 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 A<sub>3</sub> receptor (A<sub>3</sub>R) affords protection to the retina, including RGCs, unveiling the possibility for a new strategy for glaucoma treatment. Since microglial cells express A<sub>3</sub>R, we now studied the ability of a selective A<sub>3</sub>R agonist (2-Cl-IB-MECA) in controlling microglia reactivity induced by elevated hydrostatic pressure (EHP), used to mimic elevated IOP. The activation of A<sub>3</sub>R 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 A<sub>3</sub>R activation. This work demonstrates that 2-Cl-IB-MECA, the selective agonist of A<sub>3</sub>R, is able to hinder microglia reactivity, suggesting that A<sub>3</sub>R agonists could afford protection against glaucomatous degeneration through the control of neuroinflammation. |
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| id | doaj.art-71e576a0481648a6b7684001a3aa2c4b |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:56:52Z |
| publishDate | 2020-09-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-71e576a0481648a6b7684001a3aa2c4b2023-11-20T15:36:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119721810.3390/ijms21197218Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated PressureJoana Ferreira-Silva0Inês D. Aires1Raquel Boia2António Francisco Ambrósio3Ana Raquel Santiago4Coimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalCoimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalGlaucoma 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 A<sub>3</sub> receptor (A<sub>3</sub>R) affords protection to the retina, including RGCs, unveiling the possibility for a new strategy for glaucoma treatment. Since microglial cells express A<sub>3</sub>R, we now studied the ability of a selective A<sub>3</sub>R agonist (2-Cl-IB-MECA) in controlling microglia reactivity induced by elevated hydrostatic pressure (EHP), used to mimic elevated IOP. The activation of A<sub>3</sub>R 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 A<sub>3</sub>R activation. This work demonstrates that 2-Cl-IB-MECA, the selective agonist of A<sub>3</sub>R, is able to hinder microglia reactivity, suggesting that A<sub>3</sub>R agonists could afford protection against glaucomatous degeneration through the control of neuroinflammation.https://www.mdpi.com/1422-0067/21/19/7218adenosine A<sub>3</sub> receptorelevated hydrostatic pressureglaucomamicroglianeuroinflammation |
| spellingShingle | Joana Ferreira-Silva Inês D. Aires Raquel Boia António Francisco Ambrósio Ana Raquel Santiago Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure International Journal of Molecular Sciences adenosine A<sub>3</sub> receptor elevated hydrostatic pressure glaucoma microglia neuroinflammation |
| title | Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
| title_full | Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
| title_fullStr | Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
| title_full_unstemmed | Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
| title_short | Activation of Adenosine A<sub>3</sub> Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
| title_sort | activation of adenosine a sub 3 sub receptor inhibits microglia reactivity elicited by elevated pressure |
| topic | adenosine A<sub>3</sub> receptor elevated hydrostatic pressure glaucoma microglia neuroinflammation |
| url | https://www.mdpi.com/1422-0067/21/19/7218 |
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