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Title: Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage
Authors: Boia, Raquel 
Elvas, Filipe 
Madeira, Maria H. 
Aires, Inês D. 
Rodrigues-Neves, Ana C. 
Tralhão, Pedro 
Szabó, Eszter C
Baqi, Younis
Müller, Christa E. 
Tomé, Ângelo R. 
Cunha, Rodrigo A. 
Ambrósio, Francisco 
Santiago, Ana R. 
Issue Date: 5-Oct-2017
Publisher: Springer Nature
Project: The work was supported by Foundation for Science and Technology, Portugal and COMPETE-FEDER (PTDC/ BIM-MEC/0913/2012 and FCOMP-01-0124-FEDER-028417; PEst-C/SAU/UI3282- /2013 and FCOMP-01-0124-FEDER-03-7299; UID/NEU/04539/2013 and POCI-01- 0145-FEDER-007440), Centro 2020 Regional Operational Programme (CENTRO- -01-0145-FEDER-000008: BrainHealth 2020), QREN (CENTRO-07-ST24-FEDER- -002006), AIBILI and Manuel Rui Azinhais Nabeiro, Lda. 
Serial title, monograph or event: Cell Death and Disease
Volume: 8
Issue: 10
Abstract: Transient retinal ischemia is a major complication of retinal degenerative diseases and contributes to visual impairment and blindness. Evidences indicate that microglia-mediated neuroinflammation has a key role in the neurodegenerative process, prompting the hypothesis that the control of microglia reactivity may afford neuroprotection to the retina against the damage induced by ischemia-reperfusion (I-R). The available therapeutic strategies for retinal degenerative diseases have limited potential, but the blockade of adenosine A2A receptor (A2AR) emerges as candidate strategy. Therefore, we evaluated the therapeutic potential of a selective A2AR antagonist (KW6002) against the damage elicited by I-R. The administration of KW6002 after I-R injury reduced microglia reactivity and inflammatory response and afforded protection to the retina. Moreover, we tested the ability of caffeine, an adenosine receptor antagonist, in mediating protection to the retina in the I-R injury model. We demonstrated that caffeine administration dually regulated microglia reactivity and cell death in the transient retinal ischemic model, depending on the reperfusion time. At 24 h of reperfusion, caffeine increased microglial reactivity, inflammatory response and cell death elicited by I-R. However, at 7 days of reperfusion, caffeine administration decreased microglia reactivity and reduced the levels of proinflammatory cytokines and cell death. Together, these results provide a novel evidence for the use of adenosine A2AR antagonists as potential therapy for retinal ischemic diseases and demonstrate the effect of caffeine on the regulation of microglia-mediated neuroinflammation in the transient ischemic model.
ISSN: 2041-4889
DOI: 10.1038/cddis.2017.451
Rights: openAccess
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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