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The Role of the P2X7 Receptor in the Retina: Cell Signalling and Dysfunction

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 723))

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.

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References

  • Abbracchio MP, Burnstock G, Verkhratsky A et al (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32:19–29

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Bringmann A, Pannicke T, Grosche J et al (2006) Müller cells in the healthy and diseased retina. Prog Retin Eye Res 25:397–424

    Article  PubMed  CAS  Google Scholar 

  • Corriden R, Insel PA (2010) Basal release of ATP: an autocrine-paracrine mechanism for cell regulation. Sci Signal 3:re1

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Housley GD, Bringmann A, Reichenbach A (2009) Purinergic signaling in special senses. Trends Neurosci 32:128–141

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245

    Article  PubMed  CAS  Google Scholar 

  • Jo YH, Role LW (2002) Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. J Neurosci 22:4794–4804

    PubMed  CAS  Google Scholar 

  • Monif M, Burnstock G, Williams DA (2010) Microglia: proliferation and activation driven by the P2X7 receptor. Int J Biochem Cell Biol 42:1753–1756

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Newman EA (2001) Propagation of intercellular calcium waves in retinal astrocytes and Müller cells. J Neurosci 21:2215–2223

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Puthussery T, Fletcher EL (2004) Synaptic localization of P2X7 receptors in the rat retina. J Comp Neurol 472:13–23

    Article  PubMed  CAS  Google Scholar 

  • Puthussery T, Fletcher EL (2009) Extracellular ATP induces retinal photoreceptor apoptosis through activation of purinoceptors in rodents. J Comp Neurol 513:430–440

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Zhang Z, Chen G, Zhou W et al (2007) Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 9:945–953

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Kirstan A. Vessey .

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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

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