Adenosine A2A Receptor Mediated Protective Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on Retinal Ischaemia/reperfusion Damage in Rats
Overview
Authors
Affiliations
Aims: To determine the effect of 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado), an adenosine A2A receptor agonist, on retinal ischaemia/reperfusion damage in rats.
Methods: Retinal ischaemia/reperfusion damage was induced by elevating the intraocular pressure of one eye to 130 mm Hg for 60 minutes and returning it to normal. 7 days later, retinal ischaemia/reperfusion damage was histologically quantified by measuring the thickness of retinal layers. Intraocular pressure was measured by pressure transducer.
Results: Retinal ischaemia/reperfusion caused cell loss in the ganglion cell layer and thinning of the inner plexiform and nuclear layer. Both ocular topical and intravenous administration of 2-CN-Ado caused a reduction of retinal ischaemia/reperfusion damage. A selective A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine (CSC), but not a selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a selective A2B receptor antagonist, alloxazine, reduced the protective effect of 2-CN-Ado. While ocular topical administration of 2-CN-Ado caused a sustained reduction of intraocular pressure, intravenous administration of 2-CN-Ado showed a transient ocular hypotensive effect.
Conclusions: These results suggest that 2-CN-Ado attenuates retinal ischaemia/reperfusion damage, and at least some of this protective effect of 2-CN-Ado might be mediated via activation of the adenosine A2A receptor.
Pereira-Figueiredo D, Nascimento A, Cunha-Rodrigues M, Brito R, Calaza K Cell Mol Neurobiol. 2021; 42(6):1693-1725.
PMID: 33730305 PMC: 11421760. DOI: 10.1007/s10571-021-01077-4.
The effects of bevacizumab treatment in a rat model of retinal ischemia and perfusion injury.
Kohen M, Tatlipinar S, Cumbul A, Uslu U Mol Vis. 2018; 24:239-250.
PMID: 29681725 PMC: 5893009.
Role of microglia adenosine A(2A) receptors in retinal and brain neurodegenerative diseases.
Santiago A, Baptista F, Santos P, Cristovao G, Ambrosio A, Cunha R Mediators Inflamm. 2014; 2014:465694.
PMID: 25132733 PMC: 4124703. DOI: 10.1155/2014/465694.
Muthusamy A, Lin C, Shanmugam S, Lindner H, Abcouwer S, Antonetti D J Cereb Blood Flow Metab. 2014; 34(3):522-31.
PMID: 24398936 PMC: 3948134. DOI: 10.1038/jcbfm.2013.230.
Abcouwer S, Lin C, Shanmugam S, Muthusamy A, Barber A, Antonetti D J Neuroinflammation. 2013; 10:149.
PMID: 24325836 PMC: 3866619. DOI: 10.1186/1742-2094-10-149.