{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:45:27Z","timestamp":1790793927058,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Science and Technology (FCT), Portugal","award":["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)"],"award-info":[{"award-number":["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)"]}]},{"name":"FEDER-COMPETE","award":["FCOMP-01-0124-FEDER-028417 and POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["FCOMP-01-0124-FEDER-028417 and POCI-01-0145-FEDER-007440"]}]},{"name":"Centro 2020 Regional Operational Programme","award":["CENTRO-01-0145-FEDER-000008: BrainHealth 2020"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000008: BrainHealth 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms21197218","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T09:41:01Z","timestamp":1601458861000},"page":"7218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Activation of Adenosine A3 Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure"],"prefix":"10.3390","volume":"21","author":[{"given":"Joana","family":"Ferreira-Silva","sequence":"first","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas D.","family":"Aires","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0479-3066","authenticated-orcid":false,"given":"Raquel","family":"Boia","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-1641","authenticated-orcid":false,"given":"Ant\u00f3nio Francisco","family":"Ambr\u00f3sio","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"},{"name":"Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7541-7041","authenticated-orcid":false,"given":"Ana Raquel","family":"Santiago","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (ICBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal"},{"name":"Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1136\/bjophthalmol-2011-300539","article-title":"Global estimates of visual impairment: 2010","volume":"96","author":"Pascolini","year":"2012","journal-title":"Br. 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