Sustained Elevation of Extracellular ATP in Aqueous Humor from Humans with Primary Chronic Angle-closure Glaucoma

Overview

Journal Exp Eye Res

Specialty Ophthalmology

Date 2011 Jul 13

PMID 21745471

Citations 36

Authors

Ang Li

Xiulan Zhang

Danying Zheng

Jian Ge

Alan M Laties

Claire H Mitchell

Affiliations

Soon will be listed here.

Abstract

While the death of retinal ganglion cells in glaucoma is frequently associated with an elevation of intraocular pressure (IOP), the mechanisms connecting the two processes remain unclear. Extracellular ATP is released throughout the body in response to mechanical deformations. We have previously shown that patients with an acute rise in IOP have an elevated concentration of ATP in the anterior chamber. In the present study we ask whether ATP levels remain increased in patients with chronic elevations of IOP. The concentration of ATP in samples of aqueous humor obtained from patients with primary chronic angle-closure glaucoma (PCACG) was compared with that from control cataract patients whose IOP was normal. The mean ATP concentration in aqueous humor was 14-fold higher for PCACG samples than for control. ATP levels were correlated with IOP and the cup-to-disk ratio (C/D ratio). Brief treatment of Timolol, Alphagan, Pilocarpine and/or Azopt did not affect the rise in ATP concentration. In conclusion, sustained elevations in extracellular ATP levels accompany the chronic elevation of IOP in chronic glaucoma. As numerous ocular tissues express purinergic receptors, an increased extracellular ATP may have diverse physiological and pathophysiological effects.

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References

Reigada D, Lu W, Zhang M, Mitchell C . Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels. Neuroscience. 2008; 157(2):396-404. PMC: 2692262. DOI: 10.1016/j.neuroscience.2008.08.036. View

Crosson C, Yates P, Bhat A, Mukhin Y, Husain S . Evidence for multiple P2Y receptors in trabecular meshwork cells. J Pharmacol Exp Ther. 2004; 309(2):484-9. DOI: 10.1124/jpet.103.060319. View

Mitchell C, Lu W, Hu H, Zhang X, Reigada D, Zhang M . The P2X(7) receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance. Purinergic Signal. 2009; 5(2):241-9. PMC: 2686831. DOI: 10.1007/s11302-009-9142-6. View

Mitchell C, Carre D, McGlinn A, Stone R, Civan M . A release mechanism for stored ATP in ocular ciliary epithelial cells. Proc Natl Acad Sci U S A. 1998; 95(12):7174-8. PMC: 22777. DOI: 10.1073/pnas.95.12.7174. View

North R . Molecular physiology of P2X receptors. Physiol Rev. 2002; 82(4):1013-67. DOI: 10.1152/physrev.00015.2002. View

Gomes P, Srinivas S, Vereecke J, Himpens B . ATP-dependent paracrine intercellular communication in cultured bovine corneal endothelial cells. Invest Ophthalmol Vis Sci. 2004; 46(1):104-13. DOI: 10.1167/iovs.04-0846. View

Zhang X, Zhang M, Laties A, Mitchell C . Stimulation of P2X7 receptors elevates Ca2+ and kills retinal ganglion cells. Invest Ophthalmol Vis Sci. 2005; 46(6):2183-91. DOI: 10.1167/iovs.05-0052. View

Tanito M, Itai N, Dong J, Ohira A, Chihara E . Correlation between intraocular pressure level and optic disc changes in high-tension glaucoma suspects. Ophthalmology. 2003; 110(5):915-21. DOI: 10.1016/S0161-6420(03)00101-5. View

Burnstock G . Purinergic P2 receptors as targets for novel analgesics. Pharmacol Ther. 2005; 110(3):433-54. DOI: 10.1016/j.pharmthera.2005.08.013. View

10.

Luna C, Li G, Qiu J, Challa P, Epstein D, Gonzalez P . Extracellular release of ATP mediated by cyclic mechanical stress leads to mobilization of AA in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2009; 50(12):5805-10. PMC: 3140847. DOI: 10.1167/iovs.09-3796. View

11.

Hu H, Lu W, Zhang M, Zhang X, Argall A, Patel S . Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo. Exp Eye Res. 2010; 91(3):425-32. PMC: 2941978. DOI: 10.1016/j.exer.2010.06.017. View

12.

Burnstock G . Purinergic mechanosensory transduction and visceral pain. Mol Pain. 2009; 5:69. PMC: 2789721. DOI: 10.1186/1744-8069-5-69. View

13.

Li A, Leung C, Peterson-Yantorno K, Mitchell C, Civan M . Pathways for ATP release by bovine ciliary epithelial cells, the initial step in purinergic regulation of aqueous humor inflow. Am J Physiol Cell Physiol. 2010; 299(6):C1308-17. PMC: 3006323. DOI: 10.1152/ajpcell.00333.2010. View

14.

Resta V, Novelli E, Vozzi G, Scarpa C, Caleo M, Ahluwalia A . Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP. Eur J Neurosci. 2007; 25(9):2741-54. DOI: 10.1111/j.1460-9568.2007.05528.x. View

15.

Schwiebert E . ATP release mechanisms, ATP receptors and purinergic signalling along the nephron. Clin Exp Pharmacol Physiol. 2001; 28(4):340-50. DOI: 10.1046/j.1440-1681.2001.03451.x. View

16.

Gazzard G, Foster P, Devereux J, Oen F, Chew P, Khaw P . Intraocular pressure and visual field loss in primary angle closure and primary open angle glaucomas. Br J Ophthalmol. 2003; 87(6):720-5. PMC: 1771706. DOI: 10.1136/bjo.87.6.720. View

17.

Fleischhauer J, Mitchell C, Stamer W, Karl M, Peterson-Yantorno K, Civan M . Common actions of adenosine receptor agonists in modulating human trabecular meshwork cell transport. J Membr Biol. 2003; 193(2):121-36. DOI: 10.1007/s00232-002-2013-5. View

18.

Bengtsson B, Heijl A . Diurnal IOP fluctuation: not an independent risk factor for glaucomatous visual field loss in high-risk ocular hypertension. Graefes Arch Clin Exp Ophthalmol. 2005; 243(6):513-8. DOI: 10.1007/s00417-004-1103-8. View

19.

. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators. Am J Ophthalmol. 2000; 130(4):429-40. DOI: 10.1016/s0002-9394(00)00538-9. View

20.

Shahidullah M, Mandal A, Beimgraben C, Delamere N . Hyposmotic stress causes ATP release and stimulates Na,K-ATPase activity in porcine lens. J Cell Physiol. 2011; 227(4):1428-37. DOI: 10.1002/jcp.22858. View