Investigative Ophthalmology & Visual Science, Vol 37, 2603-2611, Copyright © 1996 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Involvement of adenosine in retinal ischemia. Studies on the rat

AK Larsen and NN Osborne
Nuffield Laboratory of Ophthalmology, University of Oxford, United Kingdom.

PURPOSE: The aim of this study was to determine whether adenosinergic agents can be used to slow down the changes seen in the rat retina after ischemia-reperfusion. METHODS: Ischemia-reperfusion injury to the rat retina was induced by raising the intraocular pressure above the systolic blood pressure for 45 minutes, followed by reperfusion for 3 days. This insult caused a reduction of the b-wave of the electroretinogram (54% +/- 5%, n = 23) relative to the contralateral control retina, an expression of glial fibrillary acidic protein (GFAP) in the Muller cells, and an alteration in the "staining" pattern of the calretinin immunoreactivity. The normal two to three bands of calretinin immunoreactivity in the inner plexiform layer appeared as a single band. Elevation of the intraocular pressure for 60 minutes, followed by reperfusion of 2 weeks, caused a 40% reduction in the thickness of the inner nuclear and plexiform layers. No statistically significant changes in the other retinal layers were recorded. RESULTS: When the adenosine deaminase inhibitor erythro-9-(2-hydroxyl-3- nonyl)adenine (EHNA) was injected into the eye just before ischemia, the ischemia-reperfusion changes in the b-wave and calretinin immunoreactivity were largely prevented. Similar results were observed when the adenosine A1 receptor agonist, R-N6-(2- phenylisopropyl)adenosine (R-PLA), was administered intraperitoneally just before ischemia. Injection of adenosine deaminase into the eye before ischemia seemed to potentiate the ischemia-reperfusion effect because the reduction of the b-wave was almost complete (8% +/- 4%, n = 6). The ischemia-reperfusion-induced expression of GFAP in the Muller cells was not reduced by any of the adenosinergic agents tested. This suggests that GFAP expression in the Muller cells is not related to a reduction in the b-wave. An injection of EHNA into the eye before ischemia reduced the thinning of the inner plexiform and nuclear retinal layers so that no significant difference between them and the control retinas existed. However, an injection of R-PIA just before ischemia did not reduce the thinning of the retinal layers in a statistically significant way, possibly because the R-PIA protective effect is less than that of EHNA and is difficult to detect when thickness of the retinal layers is measured. It may be necessary to use higher concentrations of R-PIA to observe a protective effect. CONCLUSIONS: The combined data show that substances resulting in the activation of adenosine A1 receptors protect the retina against changes induced by ischemia-reperfusion.

This article has been cited by other articles:

				T Konno, A Sato, T Uchibori, A Nagai, K Kogi, and N Nakahata 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., July 1, 2006; 90(7): 900 - 905. [Abstract] [Full Text] [PDF]

				K. Masuzawa, S. Jesmin, S. Maeda, Y. Kaji, T. Oshika, S. Zaedi, N. Shimojo, N. Yaji, T. Miyauchi, and K. Goto A model of retinal ischemia-reperfusion injury in rats by subconjunctival injection of endothelin-1. Experimental Biology and Medicine, June 1, 2006; 231(6): 1085 - 1089. [Abstract] [Full Text] [PDF]

				O. Uckermann, F. Kutzera, A. Wolf, T. Pannicke, A. Reichenbach, P. Wiedemann, S. Wolf, and A. Bringmann The Glucocorticoid Triamcinolone Acetonide Inhibits Osmotic Swelling of Retinal Glial Cells via Stimulation of Endogenous Adenosine Signaling J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1036 - 1045. [Abstract] [Full Text] [PDF]

				O. Uckermann, S. Uhlmann, T. Pannicke, M. Francke, R. Gamsalijew, F. Makarov, E. Ulbricht, P. Wiedemann, A. Reichenbach, N. N. Osborne, et al. Ischemia-Reperfusion Causes Exudative Detachment of the Rabbit Retina Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2592 - 2600. [Abstract] [Full Text] [PDF]

				U. Schlotzer-Schrehardt, M. Zenkel, U. Decking, D. Haubs, F. E. Kruse, A. Junemann, M. Coca-Prados, and G. O. H. Naumann Selective Upregulation of the A3 Adenosine Receptor in Eyes with Pseudoexfoliation Syndrome and Glaucoma Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 2023 - 2034. [Abstract] [Full Text] [PDF]

				B. Fortune, B. V. Bui, J. C. Morrison, E. C. Johnson, J. Dong, W. O. Cepurna, L. Jia, S. Barber, and G. A. Cioffi Selective Ganglion Cell Functional Loss in Rats with Experimental Glaucoma Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1854 - 1862. [Abstract] [Full Text] [PDF]

				E. Polska, P. Ehrlich, A. Luksch, G. Fuchsjager-Mayrl, and L. Schmetterer Effects of Adenosine on Intraocular Pressure, Optic Nerve Head Blood Flow, and Choroidal Blood Flow in Healthy Humans Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 3110 - 3114. [Abstract] [Full Text] [PDF]

				Y. Li, S. Roth, M. Laser, J.-x. Ma, and C. E. Crosson Retinal Preconditioning and the Induction of Heat-Shock Protein 27 Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1299 - 1304. [Abstract] [Full Text] [PDF]

				N. N OSBORNE, J. MELENA, G. CHIDLOW, and J. P M WOOD A hypothesis to explain ganglion cell death caused by vascular insults at the optic nerve head: possible implication for the treatment of glaucoma Br. J. Ophthalmol., October 1, 2001; 85(10): 1252 - 1259. [Full Text] [PDF]

				R. L. Gross, S. H. Hensley, F. Gao, X.-L. Yang, S.-C. Dai, and S. M. Wu Effects of Betaxolol on Light Responses and Membrane Conductance in Retinal Ganglion Cells Invest. Ophthalmol. Vis. Sci., March 1, 2000; 41(3): 722 - 728. [Abstract] [Full Text]

				G. A. Lutty, C. Merges, and D. S. McLeod 5' Nucleotidase and Adenosine during Retinal Vasculogenesis and Oxygen-Induced Retinopathy Invest. Ophthalmol. Vis. Sci., January 1, 2000; 41(1): 218 - 229. [Abstract] [Full Text]

				J. Lin and S. Roth Ischemic Preconditioning Attenuates Hypoperfusion after Retinal Ischemia in Rats Invest. Ophthalmol. Vis. Sci., November 1, 1999; 40(12): 2925 - 2931. [Abstract] [Full Text] [PDF]