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Adenosine A2A receptor mediated protective effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on retinal ischaemia/reperfusion damage in rats
  1. T Konno1,
  2. A Sato1,
  3. T Uchibori1,
  4. A Nagai1,
  5. K Kogi1,
  6. N Nakahata2
  1. 1Drug Research Section II, Fukushima Research Laboratories, Toa Eiyo Ltd, Fukushima, Japan
  2. 2Department of Cellular Signaling and 21st Century COE program “CRESCENDO”, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan
  1. Correspondence to: Takashi Konno Drug Research Section II, Fukushima Research Laboratories, Toa Eiyo Ltd, 1 Tanaka, Yuno, Iizaka, Fukushima 960-0280, Japan; konno.takashi{at}toaeiyo.co.jp

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.

  • CGS-21680, 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine
  • 2-CN-Ado, 2-(6-cyano-1-hexyn-1-yl)adenosine
  • CSC, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine
  • DMSO, dimethyl sulfoxide
  • DPCPX, 8-cyclopentyl-1,3-dipropylxanthine
  • ip, intraperitonal
  • IPL, inner plexiform layer
  • IRL, inner retinal layer
  • iv, intravenous
  • NMDA, N-methyl-d-aspartate
  • ONH, optic nerve head
  • 2-alkynyladenosine derivatives
  • adenosine A2A receptor
  • ischaemia
  • reperfusion damage
  • retina
  • intraocular pressure
  • rat
  • CGS-21680, 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine
  • 2-CN-Ado, 2-(6-cyano-1-hexyn-1-yl)adenosine
  • CSC, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine
  • DMSO, dimethyl sulfoxide
  • DPCPX, 8-cyclopentyl-1,3-dipropylxanthine
  • ip, intraperitonal
  • IPL, inner plexiform layer
  • IRL, inner retinal layer
  • iv, intravenous
  • NMDA, N-methyl-d-aspartate
  • ONH, optic nerve head
  • 2-alkynyladenosine derivatives
  • adenosine A2A receptor
  • ischaemia
  • reperfusion damage
  • retina
  • intraocular pressure
  • rat

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Footnotes

  • Competing interests: none.

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