Abstract
Adenosine 5′-triphosphate (ATP) acts as a signalling molecule within the retina. It can be released like a traditional neurotransmitter via exocytosis, but non-classical mechanisms for release have also been demonstrated. ATP and its breakdown products act at a range of purine receptor subclasses, P1, P2X and P2Y, which are expressed by all cell types of the retina. The P2X-receptors are ligand-gated ion channels and seven subclasses (P2X1-7) have been identified. In particular, the P2X7 receptor subclass is unique; it is relatively insensitive to ATP and it has a long intracellular C-terminus, which is not only critical for ion channel function, but also allows the formation of a pore in the plasma membrane following prolonged stimulation with ATP, which is permeable to molecules up to 900 kDa. This unique activity means the P2X7 receptor has been found to be involved in a range of physiological and pathological roles. In the retina, the receptor is expressed by neurons, macroglia and microglia. This review focuses on the role of the P2X7 receptor in these retinal tissues under physiological conditions and during disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abbracchio MP, Burnstock G, Verkhratsky A et al (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32:19–29
Bringmann A, Pannicke T, Uhlmann S et al (2002) Membrane conductance of Müller glial cells in proliferative diabetic retinopathy. Can J Ophthalmol 37:221–227
Bringmann A, Pannicke T, Moll V et al (2001) Upregulation of P2X(7) receptor currents in Müller glial cells during proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 42:860–867
Bringmann A, Pannicke T, Grosche J et al (2006) Müller cells in the healthy and diseased retina. Prog Retin Eye Res 25:397–424
Corriden R, Insel PA (2010) Basal release of ATP: an autocrine-paracrine mechanism for cell regulation. Sci Signal 3:re1
Ferrari D, Los M, Bauer MK et al (1999) P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death. FEBS Lett 447:71–75
Franke H, Klimke K, Brinckmann U et al (2005) P2X(7) receptor-mRNA and -protein in the mouse retina; changes during retinal degeneration in BALBCrds mice. Neurochem Int 47:235–242
Housley GD, Bringmann A, Reichenbach A (2009) Purinergic signaling in special senses. Trends Neurosci 32:128–141
Hu H, Lu W, Zhang M et al (2010) Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo. Exp Eye Res 91:425–432
Innocenti B, Pfeiffer S, Zrenner E et al (2004) ATP-induced non-neuronal cell permeabilization in the rat inner retina. J Neurosci 24:8577–8583
Ishii K, Kaneda M, Li H et al (2003) Neuron-specific distribution of P2X7 purinergic receptors in the monkey retina. J Comp Neurol 459:267–277
Jabs R, Guenther E, Marquordt K et al (2000) Evidence for P2X(3), P2X(4), P2X(5) but not for P2X(7) containing purinergic receptors in Müller cells of the rat retina. Brain Res Mol Brain Res 76:205–210
Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245
Jo YH, Role LW (2002) Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. J Neurosci 22:4794–4804
Monif M, Burnstock G, Williams DA (2010) Microglia: proliferation and activation driven by the P2X7 receptor. Int J Biochem Cell Biol 42:1753–1756
Monif M, Reid CA, Powell KL et al (2009) The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J Neurosci 29:3781–3791
Morigiwa K, Quan M, Murakami M et al (2000) P2 Purinoceptor expression and functional changes of hypoxia-activated cultured rat retinal microglia. Neurosci Lett 282:153–156
Newman EA (2001) Propagation of intercellular calcium waves in retinal astrocytes and Müller cells. J Neurosci 21:2215–2223
Pearson RA, Dale N, Llaudet E et al (2005) ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation. Neuron 46:731–744
Puthussery T, Fletcher EL (2004) Synaptic localization of P2X7 receptors in the rat retina. J Comp Neurol 472:13–23
Puthussery T, Fletcher EL (2009) Extracellular ATP induces retinal photoreceptor apoptosis through activation of purinoceptors in rodents. J Comp Neurol 513:430–440
Puthussery T, Yee P, Vingrys AJ et al (2006) Evidence for the involvement of purinergic P2X receptors in outer retinal processing. Eur J Neurosci 24:7–19
Resta V, Novelli E, Vozzi G et al (2007) Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP. Eur J Neurosci 25:2741–2754
Ricatti MJ, Alfie LD, Lavoie EG et al (2009) Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse and zebrafish. Synapse 63:291–307
Surprenant A, Rassendren F, Kawashima E et al (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272:735–738
Ward MM, Puthussery T, Vessey KA et al (2010) The role of purinergic receptors in retinal function and disease. Adv Exp Med Biol 664:385–391
Wheeler-Schilling TH, Marquordt K, Kohler K et al (2001) Identification of purinergic receptors in retinal ganglion cells. Brain Res Mol Brain Res 92:177–180
Zhang X, Zhang M, Laties AM et al (2005) Stimulation of P2X7 receptors elevates Ca2+ and kills retinal ganglion cells. Invest Ophthalmol Vis Sci 46:2183–2191
Zhang Z, Chen G, Zhou W et al (2007) Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 9:945–953
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this paper
Cite this paper
Vessey, K.A., Jobling, A.I., Greferath, U., Fletcher, E.L. (2012). The Role of the P2X7 Receptor in the Retina: Cell Signalling and Dysfunction. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_104
Download citation
DOI: https://doi.org/10.1007/978-1-4614-0631-0_104
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-0630-3
Online ISBN: 978-1-4614-0631-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)