Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/106203 https://doi.org/10.3390/ijms21197218 |
Resumo: | 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. |
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Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressureadenosine A3 receptorelevated hydrostatic pressureglaucomamicroglianeuroinflammationGlaucoma 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.This work was supported by Foundation for Science and Technology (FCT), Portugal (Fellowships PD/BD/114115/2015 and PD/BD/127821/2016, Grant PTDC/NEU-OSD/3123/2014; Strategic Projects UID/NEU/04539/2019 (CNC.IBILI) and UIDB/04539/2020; and UIDP/04539/2020 (CIBB)), FEDER-COMPETE (FCOMP-01-0124-FEDER-028417 and POCI-01-0145-FEDER-007440), and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020).MDPI2020-09-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106203http://hdl.handle.net/10316/106203https://doi.org/10.3390/ijms21197218eng1422-0067330078351422-0067Ferreira-Silva, JoanaAires, Inês D.Boia, RaquelAmbrósio, António FranciscoSantiago, Ana Raquelinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-06T10:20:21Zoai:estudogeral.uc.pt:10316/106203Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:41.549872Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
title |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
spellingShingle |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure Ferreira-Silva, Joana adenosine A3 receptor elevated hydrostatic pressure glaucoma microglia neuroinflammation |
title_short |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
title_full |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
title_fullStr |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
title_full_unstemmed |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
title_sort |
Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure |
author |
Ferreira-Silva, Joana |
author_facet |
Ferreira-Silva, Joana Aires, Inês D. Boia, Raquel Ambrósio, António Francisco Santiago, Ana Raquel |
author_role |
author |
author2 |
Aires, Inês D. Boia, Raquel Ambrósio, António Francisco Santiago, Ana Raquel |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Ferreira-Silva, Joana Aires, Inês D. Boia, Raquel Ambrósio, António Francisco Santiago, Ana Raquel |
dc.subject.por.fl_str_mv |
adenosine A3 receptor elevated hydrostatic pressure glaucoma microglia neuroinflammation |
topic |
adenosine A3 receptor elevated hydrostatic pressure glaucoma microglia neuroinflammation |
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 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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-09-30 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/106203 http://hdl.handle.net/10316/106203 https://doi.org/10.3390/ijms21197218 |
url |
http://hdl.handle.net/10316/106203 https://doi.org/10.3390/ijms21197218 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1422-0067 33007835 1422-0067 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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