Investigative Ophthalmology & Visual Science, Vol 37, 1-10, Copyright © 1996 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Adenosine promotes regulation of corneal hydration through cyclic adenosine monophosphate

MV Riley, BS Winkler, CA Starnes and MI Peters
Eye Research Institute, Oakland University, Rochester, MI 48309-4401, USA.

PURPOSE. To investigate the cellular mechanisms whereby adenosine increases net transendothelial fluid transport by the endothelial cells of the cornea. METHODS. Rabbit corneas were isolated and the endothelial surface was superfused while thickness was measured with the specular microscope. Cyclic adenosine monophosphate (cAMP) was measured in endothelia from fresh and incubated corneas, and adenylyl cyclase and phosphodiesterase activities were measured in homogenates or the particulate fraction of endothelia from bovine or rabbit. Adenosine, adenosine-receptor agonists, dibutyryl cAMP, forskolin, and phosphodiesterase inhibitors were used to modulate physiological and biochemical parameters. RESULTS. Adenosine, N- ethyl(carboxamido)adenosine, dibutyryl cAMP, forskolin, and phosphodiesterase inhibitors all promoted deturgescence of swollen corneas and maintained fresh corneas at lower steady state thicknesses than in controls. These effects were abolished in the presence of ouabain or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid or after complete removal of HCO3- from the media. Intracellular cAMP was significantly increased by forskolin and phosphodiesterase inhibitors and, to a lesser extent, by agonists. Increases in cAMP concentration declined rapidly with time. Cyclase activity in the bovine tissue was enhanced by agonists and by G-protein activators. Dose-response curves of corneal swelling indicated a greater sensitivity to N- ethyl(carboxamido)adenosine than to the A2 alpha specific agonist CGS 21680. CONCLUSIONS. Adenosine increases net endothelial fluid transport through an increase in cAMP. The effects are mediated by stimulation of adenylyl cyclase through a G-protein coupled to an adenosine receptor, which is most probably of the A2 beta subtype. Results suggest that the regulation of corneal hydration by adenosine is more probably through stimulation of active transport than through a change in permeability, involving either transmembrane fluxes of Na+ or HCO3- or another step tightly coupled to these primary events in fluid movement.

This article has been cited by other articles:

				C. D'hondt, S. P. Srinivas, J. Vereecke, and B. Himpens Adenosine Opposes Thrombin-Induced Inhibition of Intercellular Calcium Wave in Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1518 - 1527. [Abstract] [Full Text] [PDF]

				S. P. Srinivas, M. Satpathy, Y. Guo, and V. Anandan Histamine-Induced Phosphorylation of the Regulatory Light Chain of Myosin II Disrupts the Barrier Integrity of Corneal Endothelial Cells. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 4011 - 4018. [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]

				J. Li, X. C. Sun, and J. A. Bonanno Role of NBC1 in apical and basolateral HCO3- permeabilities and transendothelial HCO3- fluxes in bovine corneal endothelium Am J Physiol Cell Physiol, March 1, 2005; 288(3): C739 - C746. [Abstract] [Full Text] [PDF]

				P. Gomes, S. P. Srinivas, J. Vereecke, and B. Himpens ATP-Dependent Paracrine Intercellular Communication in Cultured Bovine Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 104 - 113. [Abstract] [Full Text] [PDF]

				X. C. Sun, C.-B. Zhai, M. Cui, Y. Chen, L. R. Levin, J. Buck, and J. A. Bonanno HCO-3-dependent soluble adenylyl cyclase activates cystic fibrosis transmembrane conductance regulator in corneal endothelium Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1114 - C1122. [Abstract] [Full Text] [PDF]

				Y. Zhang, Q. Xie, X. C. Sun, and J. A. Bonanno Enhancement of HCO3- Permeability across the Apical Membrane of Bovine Corneal Endothelium by Multiple Signaling Pathways Invest. Ophthalmol. Vis. Sci., April 1, 2002; 43(4): 1146 - 1153. [Abstract] [Full Text] [PDF]

				S. Narravula, P. F. Lennon, B. U. Mueller, and S. P. Colgan Regulation of Endothelial CD73 by Adenosine: Paracrine Pathway for Enhanced Endothelial Barrier Function J. Immunol., November 1, 2000; 165(9): 5262 - 5268. [Abstract] [Full Text] [PDF]

				S. Jelamskii, X. C. Sun, P. Herse, and J. A. Bonanno Basolateral Na+-K+-2Cl- Cotransport in Cultured and Fresh Bovine Corneal Endothelium Invest. Ophthalmol. Vis. Sci., February 1, 2000; 41(2): 488 - 495. [Abstract] [Full Text]

				L. S. Engel, J. M. Hill, A. R. Caballero, L. C. Green, and R. J. O'Callaghan Protease IV, a Unique Extracellular Protease and Virulence Factor from Pseudomonas aeruginosa J. Biol. Chem., July 3, 1998; 273(27): 16792 - 16797. [Abstract] [Full Text] [PDF]

				M. V. Riley, B. S. Winkler, C. A. Starnes, and M. I. Peters Fluid and ion transport in corneal endothelium: insensitivity to modulators of Na+-K+-2Cl- cotransport Am J Physiol Cell Physiol, November 1, 1997; 273(5): C1480 - C1486. [Abstract] [Full Text] [PDF]

				J. FISCHBARG Mechanism of fluid transport across corneal endothelium and other epithelial layers: a possible explanation based on cyclic cell volume regulatory changes Br. J. Ophthalmol., January 1, 1997; 81(1): 85 - 89. [Full Text] [PDF]

				X. C. Sun and J. A. Bonanno Expression, localization, and functional evaluation of CFTR in bovine corneal endothelial cells Am J Physiol Cell Physiol, April 1, 2002; 282(4): C673 - C683. [Abstract] [Full Text] [PDF]