%0 Journal Article
%T Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage
%A Ana C Rodrigues-Neves
%A Ana R Santiago
%A Ant車nio F Ambr車sio
%A Christa E M邦ller
%A Eszter C Szab車
%A Filipe Elvas
%A In那s D Aires
%A Maria H Madeira
%A Pedro Tralhˋo
%A Raquel Boia
%A Rodrigo A Cunha
%A Younis Baqi
%A ˋngelo R Tom谷
%J Archive of "Cell Death & Disease".
%D 2017
%R 10.1038/cddis.2017.451
%X 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每reperfusion (I每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每R. The administration of KW6002 after I每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每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 24ˋh of reperfusion, caffeine increased microglial reactivity, inflammatory response and cell death elicited by I每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
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680573/