Adenosine A2A receptor mediated protective effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on retinal ischaemia/reperfusion damage in rats

Br J Ophthalmol. 2006 Jul;90(7):900-5. doi: 10.1136/bjo.2006.091496. Epub 2006 Apr 13.

Abstract

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.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Adenosine / therapeutic use
  • Adenosine A2 Receptor Agonists*
  • Administration, Topical
  • Animals
  • Antihypertensive Agents / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Intraocular Pressure / drug effects
  • Ischemic Preconditioning*
  • Male
  • Phenethylamines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology*

Substances

  • 2-(6-cyano-1-hexyn-1-yl)adenosine
  • Adenosine A2 Receptor Agonists
  • Antihypertensive Agents
  • Excitatory Amino Acid Antagonists
  • Phenethylamines
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Dizocilpine Maleate
  • Adenosine