Advertisement

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

  • Kirstan A. VesseyEmail author
  • Andrew I. Jobling
  • Ursula Greferath
  • Erica L. Fletcher
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Adenosine 5′-triphosphate (ATP) Purine receptor P2X7 receptor Retina Photoreceptors Ganglion cells Müller cells Microglia 

References

  1. Abbracchio MP, Burnstock G, Verkhratsky A et al (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32:19–29PubMedCrossRefGoogle Scholar
  2. Bringmann A, Pannicke T, Uhlmann S et al (2002) Membrane conductance of Müller glial cells in proliferative diabetic retinopathy. Can J Ophthalmol 37:221–227PubMedGoogle Scholar
  3. 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 42:860–867PubMedGoogle Scholar
  4. Bringmann A, Pannicke T, Grosche J et al (2006) Müller cells in the healthy and diseased retina. Prog Retin Eye Res 25:397–424PubMedCrossRefGoogle Scholar
  5. Corriden R, Insel PA (2010) Basal release of ATP: an autocrine-paracrine mechanism for cell regulation. Sci Signal 3:re1Google Scholar
  6. 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 447:71–75PubMedCrossRefGoogle Scholar
  7. 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 47:235–242PubMedCrossRefGoogle Scholar
  8. Housley GD, Bringmann A, Reichenbach A (2009) Purinergic signaling in special senses. Trends Neurosci 32:128–141PubMedCrossRefGoogle Scholar
  9. Hu H, Lu W, Zhang M et al (2010) Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo. Exp Eye Res 91:425–432PubMedCrossRefGoogle Scholar
  10. Innocenti B, Pfeiffer S, Zrenner E et al (2004) ATP-induced non-neuronal cell permeabilization in the rat inner retina. J Neurosci 24:8577–8583PubMedCrossRefGoogle Scholar
  11. Ishii K, Kaneda M, Li H et al (2003) Neuron-specific distribution of P2X7 purinergic receptors in the monkey retina. J Comp Neurol 459:267–277PubMedCrossRefGoogle Scholar
  12. 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 76:205–210PubMedCrossRefGoogle Scholar
  13. Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245PubMedCrossRefGoogle Scholar
  14. Jo YH, Role LW (2002) Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. J Neurosci 22:4794–4804PubMedGoogle Scholar
  15. Monif M, Burnstock G, Williams DA (2010) Microglia: proliferation and activation driven by the P2X7 receptor. Int J Biochem Cell Biol 42:1753–1756PubMedCrossRefGoogle Scholar
  16. 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 29:3781–3791PubMedCrossRefGoogle Scholar
  17. Morigiwa K, Quan M, Murakami M et al (2000) P2 Purinoceptor expression and functional changes of hypoxia-activated cultured rat retinal microglia. Neurosci Lett 282:153–156PubMedCrossRefGoogle Scholar
  18. Newman EA (2001) Propagation of intercellular calcium waves in retinal astrocytes and Müller cells. J Neurosci 21:2215–2223PubMedGoogle Scholar
  19. 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 46:731–744PubMedCrossRefGoogle Scholar
  20. Puthussery T, Fletcher EL (2004) Synaptic localization of P2X7 receptors in the rat retina. J Comp Neurol 472:13–23PubMedCrossRefGoogle Scholar
  21. Puthussery T, Fletcher EL (2009) Extracellular ATP induces retinal photoreceptor apoptosis through activation of purinoceptors in rodents. J Comp Neurol 513:430–440PubMedCrossRefGoogle Scholar
  22. Puthussery T, Yee P, Vingrys AJ et al (2006) Evidence for the involvement of purinergic P2X receptors in outer retinal processing. Eur J Neurosci 24:7–19PubMedCrossRefGoogle Scholar
  23. 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 25:2741–2754PubMedCrossRefGoogle Scholar
  24. Ricatti MJ, Alfie LD, Lavoie EG et al (2009) Immunocytochemical localization of NTPDases1 and 2 in the neural retina of mouse and zebrafish. Synapse 63:291–307PubMedCrossRefGoogle Scholar
  25. Surprenant A, Rassendren F, Kawashima E et al (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272:735–738PubMedCrossRefGoogle Scholar
  26. Ward MM, Puthussery T, Vessey KA et al (2010) The role of purinergic receptors in retinal function and disease. Adv Exp Med Biol 664:385–391PubMedCrossRefGoogle Scholar
  27. Wheeler-Schilling TH, Marquordt K, Kohler K et al (2001) Identification of purinergic receptors in retinal ganglion cells. Brain Res Mol Brain Res 92:177–180PubMedCrossRefGoogle Scholar
  28. Zhang X, Zhang M, Laties AM et al (2005) Stimulation of P2X7 receptors elevates Ca2+ and kills retinal ganglion cells. Invest Ophthalmol Vis Sci 46:2183–2191PubMedCrossRefGoogle Scholar
  29. Zhang Z, Chen G, Zhou W et al (2007) Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 9:945–953PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kirstan A. Vessey
    • 1
    Email author
  • Andrew I. Jobling
    • 1
  • Ursula Greferath
    • 1
  • Erica L. Fletcher
    • 1
  1. 1.Department of Anatomy and Cell BiologyThe University of MelbourneMelbourneAustralia

Personalised recommendations