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 language | English |
|---|---|
| Article number | e3065 |
| Journal | Cell Death and Disease |
| Volume | 8 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage
AU - Boia, Raquel
AU - Elvas, Filipe
AU - Madeira, Maria H.
AU - Aires, Inês D.
AU - Rodrigues-Neves, Ana C.
AU - Tralhão, Pedro
AU - Szabó, Eszter C.
AU - Baqi, Younis
AU - Müller, Christa E.
AU - Tomé, Ângelo R.
AU - Cunha, Rodrigo A.
AU - Ambrósio, António F.
AU - Santiago, Ana R.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041823993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041823993&partnerID=8YFLogxK
U2 - 10.1038/cddis.2017.451
DO - 10.1038/cddis.2017.451
M3 - Article
AN - SCOPUS:85041823993
VL - 8
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 10
M1 - e3065
ER -