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The P2X7 receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance

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Abstract

Retinal ganglion cells process the visual signal and transmit it along their axons in the optic nerve to the brain. Molecular, immunohistochemical, and functional analyses indicate that the majority of retinal ganglion cells express the ionotropic P2X7 receptor. Stimulation of the receptor can lead to a rise in intracellular calcium and cell death, although death does not involve the opening of a large diameter pore. Adenosine acting at A3 receptors can attenuate the rise in calcium and death accompanying P2X7 receptor activation, suggesting that dephosphorylation of ATP into adenosine is neuroprotective and that the balance of extracellular purines can influence neuronal survival. Increased intraocular pressure can lead to release of excessive extracellular ATP in the retina and damage ganglion cells by acting on P2X7 receptors, implicating a role for the receptor in the loss of ganglion cell activity in glaucoma. In summary, the activation of P2X7 receptors has both physiologic and pathophysiologic implications for ganglion cell function. These characteristics may also provide an insight into the contributions the P2X7 receptor makes to neurons elsewhere.

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Acknowledgements

This work was supported by grants EY-015537 and EY-013434 from the NIH to CHM, and EY-01583 to the Vision Research Center of the University of Pennsylvania, by a University Research Foundation award from the University of Pennsylvania to CHM, by the Jody Sack Fund to XZ, MZ, and HH. The authors would like to thank Alan Laties for many useful discussions.

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Authors and Affiliations

  1. Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA, 19104–6085, USA

    Claire H. Mitchell & Wennan Lu

  2. Department of Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104–6085, USA

    Huiling Hu & Mei Zhang

  3. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China

    Huiling Hu & Xiulan Zhang

  4. Instituto Cajal, CSIC, Madrid, Spain

    David Reigada

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  1. Claire H. Mitchell
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  2. Wennan Lu
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  4. Xiulan Zhang
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Correspondence to Claire H. Mitchell.

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This article has previously been published in issue 4/4, under doi10.1007/s11302-008-9125-z.

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Mitchell, C.H., Lu, W., Hu, H. et al. The P2X7 receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance. Purinergic Signalling 5, 241–249 (2009). https://doi.org/10.1007/s11302-009-9142-6

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  • DOI: https://doi.org/10.1007/s11302-009-9142-6

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