Open AccessTreatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage
Author(s) -
Raquel Boia,
Filipe Elvas,
Maria Madeira,
Inês Aires,
Ana Catarina RodriguesNeves,
Pedro Tralhão,
Eszter Szabó,
Younis Baqi,
Christa E. Müller,
Ângelo R. Tomé,
Rodrigo A. Cunha,
António Francisco Ambrósio,
Ana Raquel Santiago
Publication year - 2017
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/cddis.2017.451
Subject(s) - microglia , neuroinflammation , neuroprotection , adenosine a2a receptor , adenosine receptor antagonist , pharmacology , retina , adenosine receptor , retinal , antagonist , proinflammatory cytokine , medicine , adenosine , neuroscience , receptor , immunology , inflammation , biology , ophthalmology , agonist
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 A 2A receptor (A 2A R) emerges as candidate strategy. Therefore, we evaluated the therapeutic potential of a selective A 2A R 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 A 2A R 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.