Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/91058
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dc.contributor.authorInês Dinis Aires-
dc.contributor.authorMaria Helena Madeira-
dc.contributor.authorRaquel Boia-
dc.contributor.authorAna Catarina Rodrigues-Neves-
dc.contributor.authorJoana Margarida Martins-
dc.contributor.authorAntónio Francisco Ambrósio-
dc.contributor.authorAna Raquel Santiago-
dc.date.accessioned2020-09-15T15:17:01Z-
dc.date.available2020-09-15T15:17:01Z-
dc.date.issued2019-11-20-
dc.identifier.issn2045-2322pt
dc.identifier.urihttp://hdl.handle.net/10316/91058-
dc.description.abstractDiabetic retinopathy is a major complication of diabetes mellitus and a leading cause of blindness. The pathogenesis of diabetic retinopathy is accompanied by chronic low-grade inflammation. Evidence shows that the blockade of adenosine A2A receptors (A2AR) affords protection to the retina through the control of microglia-mediated neuroinflammation. Herein, we investigated the therapeutic potential of an antagonist of A2AR in a model of diabetic retinopathy. Type 1 diabetes was induced in 4-5 months old C57BL/6 J mice with a single intraperitoneal injection streptozotocin. Animals were treated one month after the onset of diabetes. The A2AR antagonist was delivered by intravitreal injection once a week for 4 weeks. Microglia reactivity and inflammatory mediators were increased in the retinas of diabetic animals. The treatment with the A2AR antagonist was able to control microglial reactivity and halt neuroinflammation. Furthermore, the A2AR antagonist rescued retinal vascular leakage, attenuated alterations in retinal thickness, decreased retinal cell death and the loss of retinal ganglion cells induced by diabetes. These results demonstrate that intravitreal injection of the A2AR antagonist controls inflammation, affords protection against cell loss and reduces vascular leakage associated with diabetes, which could be envisaged as a therapeutic approach for the early complications of diabetes in the retina.pt
dc.description.sponsorshipGlobal Ophthalmology Awards Program from Bayer 2015 (US2083156314). Foundation for Science and Technology (FCT), Portugal, and COMPETE-FEDER: PTDC/BIM-MEC/0913/2012; PTDC/NEU-OSD/3123/2014; FCOMP-01-0124-FEDER-028417; UID/NEU/04539/2013, UID/NEU/04539/2019 and POCI-01-0145-FEDER-007440); FCT PhD fellowships PD/BD/127821/2016 and PD/BD/114115/2015; Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BRAINHEALTH 2020)pt
dc.language.isoengpt
dc.publisherNATURE PUBLISHING GROUPpt
dc.relationBayer AGpt
dc.relationEuropean Union (EU)pt
dc.relationPortuguese Foundation for Science and Technologypt
dc.relationCentro 2020 Regional Operational Programme (BRAINHEALTH 2020)pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt
dc.subjectNitric-Oxide Synthasept
dc.subjectGanglion-Cellspt
dc.subjectMicroglial activationpt
dc.subjectRetinopathypt
dc.subjectRatpt
dc.subjectInflammationpt
dc.subjectModelpt
dc.subjectNeurodegenerationpt
dc.subjectDegenerationpt
dc.subjectApoptosispt
dc.titleIntravitreal injection of adenosine A2A receptor antagonist reduces neuroinflammation, vascular leakage and cell death in the retina of diabetic micept
dc.typearticle-
degois.publication.issue17207pt
degois.publication.locationMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDpt
degois.publication.titleScientific Reportspt
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-019-53627-ypt
dc.peerreviewedyespt
dc.identifier.doi10.1038/s41598-019-53627-ypt
degois.publication.volume9pt
dc.date.embargo2019-11-20*
uc.date.periodoEmbargo0pt
item.languageiso639-1en-
item.grantfulltextopen-
item.fulltextCom Texto completo-
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
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