Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage

Raquel Boia, Filipe Elvas, Maria H. Madeira, Inês D. Aires, Ana C. Rodrigues-Neves, Pedro Tralhão, Eszter C. Szabó, Younis Baqi, Christa E. Müller, Ângelo R. Tomé, Rodrigo A. Cunha, António F. Ambrósio, Ana R. Santiago

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Article numbere3065
JournalCell Death and Disease
Volume8
Issue number10
DOIs
Publication statusPublished - Jan 1 2017

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Microglia
Caffeine
Retina
Retinal Diseases
Reperfusion
Cell Death
Reperfusion Injury
Ischemia
Adenosine A2 Receptor Antagonists
Adenosine A2A Receptors
Purinergic P1 Receptor Antagonists
Vision Disorders
Blindness
Therapeutics
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage. / 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, António F.; Santiago, Ana R.

In: Cell Death and Disease, Vol. 8, No. 10, e3065, 01.01.2017.

Research output: Contribution to journalArticle

Boia, R, Elvas, F, Madeira, MH, Aires, ID, Rodrigues-Neves, AC, Tralhão, P, Szabó, EC, Baqi, Y, Müller, CE, Tomé, ÂR, Cunha, RA, Ambrósio, AF & Santiago, AR 2017, 'Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage', Cell Death and Disease, vol. 8, no. 10, e3065. https://doi.org/10.1038/cddis.2017.451
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, António F. ; Santiago, Ana R. / Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage. In: Cell Death and Disease. 2017 ; Vol. 8, No. 10.
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