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N-Methyl-d-aspartate receptors in the retina

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Abstract

The vertebrate retina is a “genuine neural center” (Ramón y Cajal), in which glutamate is a major excitatory neurotransmitter. Both N-methyl-d-aspartate (NMDA) and non-NMDA receptors are expressed in the retina. Although non-NMDA receptors and/or metabotropic glutamate receptors are generally thought to be responsible for mediating the transfer of visual signals in the outer retina, there is recent evidence suggesting that NMDA receptors are also expressed in photoreceptors, as well as horizontal and bipolar cells. In the inner retina, NMDA receptors, in addition to other glutamate receptor subtypes, are abundantly expressed to mediate visual signal transmission from bipolar cells to amacrine and ganglion cells, and could be involved in modulation of inhibitory feedback from amacrine cells to bipolar cells. NMDA receptors are extrasynaptically expressed in ganglion cells (and probably amacrine cells) and may play physiological roles in a special mode. Activity of NMDA receptors may be modulated by neuromodulators, such as d-serine and others. This article discusses retinal excitotoxicity mediated by NMDA receptors.

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References

  1. Miyachi, E., Hidaka, S., and Murakami M. (1999) Electrical couplings of retinal neurons. In The Retinal Basis of Vision. Toyada J., Murakami M., Kaneko A., Saito T., eds, Elsevier Science B.V. Amsterdam, pp. 171–184.

    Google Scholar 

  2. Thoreson W. B. and, Witkovsky P. (1999) Glutamate receptors and circuits in the vertebrate retina. Prog. Retin. Eye Res. 18, 765–810.

    Article  PubMed  CAS  Google Scholar 

  3. Yang X. L. (2004) Characterization of receptors for glutamate and GABA in retinal neurons. Prog. Neurobiol. 73, 127–150.

    Article  PubMed  CAS  Google Scholar 

  4. Ozawa S., Kamiya H., and Tsuzuki K. (1998) Glutamate receptors in the mammalian central nervous system. Prog. Neurobiol. 54, 581–618.

    Article  PubMed  CAS  Google Scholar 

  5. Dingledine R., Borges K., Bowie D. and Traynelis S. F. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61.

    PubMed  CAS  Google Scholar 

  6. Dowling J. E. (1987) The Retina: An Approachable Part of the Brain. Cambridge: The Belknap Press of the Harvard University Press.

    Google Scholar 

  7. Newman E. and Reichenbach A. (1996) The Müller cell: a functional element of the retina. Trends Neurosci. 19, 307–312.

    Article  PubMed  CAS  Google Scholar 

  8. Hasegawa J., Obara T., Tanaka K., and Tachibana M. (2006) High-density presynaptic transporters are required for glutamate removal from the first visual synapse. Neuron 50, 63–74.

    Article  PubMed  CAS  Google Scholar 

  9. Cull-Candy S., Brickley S., and Farrant M. (2001) NMDA receptor subunits: diversity, development and disease. Curr. Opin. Neurobiol. 11, 327–335.

    Article  PubMed  CAS  Google Scholar 

  10. Haddad J. J. (2005) N-methyl-D-aspartate (NMDA) and the regulation of mitogen-activated protein kinase (MAPK) signaling pathways: a revolving neurochemical axis for therapeutic intervention? Prog. Neurobiol. 77, 252–282.

    PubMed  CAS  Google Scholar 

  11. McBain C. J. and Mayer M. L. (1994) N-methyl-D-aspartic acid receptor structure and function. Physiol. Rev. 74, 723–760.

    PubMed  CAS  Google Scholar 

  12. Michaelis E. K. (1998) Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog. Neurobiol. 54, 369–415.

    Article  PubMed  CAS  Google Scholar 

  13. Nong, Y., Huang Y. Q., and Salter M. W. (2004) NMDA receptors are movin' in. Curr. Opin. Neurobiol. 14, 353–361.

    Article  PubMed  CAS  Google Scholar 

  14. Lipton S. A. (2003) Possible role for memantine in protecting retinal ganglion cells from glaucomatous damage. Surv. Ophthalmol. 48 48 (Suppl 1), S38-S46.

    Article  PubMed  Google Scholar 

  15. Lipton S. A. (2001) Retinal ganglion cells, glaucoma and neuroprotection. Prog. Brain Res. 131, 712–718.

    PubMed  CAS  Google Scholar 

  16. Kalloniatis M. and, Tomisich G. (1999) Amino acid neurochemistry of the vertebrate retina. Prog. Retin. Eye Res. 18, 811–866.

    Article  PubMed  CAS  Google Scholar 

  17. Bliss T. V. and, Collingridge G. L. (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39.

    Article  PubMed  CAS  Google Scholar 

  18. Carroll R. C. and Zukin R. S. (2002) NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity. Trends Neurosci. 25, 571–577.

    Article  PubMed  CAS  Google Scholar 

  19. Li B., Chen N., Luo T., Otsu Y., Murphy T. H., and Raymond L. A. (2002) Differential regulation of synaptic and extra-synaptic NMDA receptors. Nat. Neurosci. 5, 833–834.

    Article  PubMed  CAS  Google Scholar 

  20. Monyer H., Burnashev N., Laurie D. J., Sakmann B., and Seeburg P. H. (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529–540.

    Article  PubMed  CAS  Google Scholar 

  21. Prybylowski K., Fu Z., Losi G., et al. (2002) Relationship between availability of NMDA receptor subunits and their expression at the synapse. J Neurosci. 22, 8902–8910.

    PubMed  CAS  Google Scholar 

  22. Sucher N. J., Kohler K., Tenneti L., et al. (2003) N-methyl-D-aspartate receptor subunit NR3A in the retina: developmental expression, cellular localization, and functional aspects. Invest. Ophthalmol. Vis. Sci. 44, 4451–4456.

    Article  PubMed  Google Scholar 

  23. Prybylowski K. and, Wenthold R. J. (2004) N-Methyl-D-aspartate receptors: subunit assembly and trafficking to the synapse. J. Biol. Chem. 279, 9673–9676.

    Article  PubMed  CAS  Google Scholar 

  24. Durand G. M., Gregor P., Zheng X., Bennett M. V., Uhl G. R., and Zukin R. S. (1992) Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to polyamines and activators of protein kinase C. Proc. Natl. Acad. Sci. USA 89, 9359–9363.

    Article  PubMed  CAS  Google Scholar 

  25. Sugihara H., Moriyoshi K., Ishii T., Masu M., and Nakanishi S. (1992) Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing, Biochem. Biophys. Res. Commun. 185, 826–832.

    Article  PubMed  CAS  Google Scholar 

  26. Das S., Sasaki Y. F., Rothe T., et al. (1998) Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 393, 377–381.

    Article  PubMed  CAS  Google Scholar 

  27. Chazot P. L. (2004) The NMDA receptor NR2B subunit: a valid therapeutic target for multiple CNS pathologies. Curr. Med. Chem. 11, 389–396.

    Article  PubMed  CAS  Google Scholar 

  28. Luo J., Wang Y., Yasuda R. P., Dunah A. W., and Wolfe B. B. (1997) The majority of N-methyl-D-aspartate receptor complexes in adult rat cerebral cortex contain at least three different subunits (NR1/NR2A/NR2B). Mol. Pharmacol. 51, 79–86.

    PubMed  CAS  Google Scholar 

  29. Cline H. T. and Tsien R. W. (1991) Glutamate-induced increased in intracellular Ca2+ in cultured frog tectal cells mediated by direct activation of NMDA receptor channels. Neuron 6, 259–267.

    Article  PubMed  CAS  Google Scholar 

  30. MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., and Barker J. L. (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature 321, 519–522.

    Article  PubMed  CAS  Google Scholar 

  31. Siliprandi R., Canella R., Carmignoto G., et al. (1992) N-methyl-D-aspartate-induced neurotoxicity in the adult rat retina. Vis. Neurosci. 8, 567–573.

    PubMed  CAS  Google Scholar 

  32. Sucher N. J., Wong L. A., and Lipton S. A. (1990) Redox modulation of NMDA receptor-mediated Ca2+ flux in mammalian central neurons. Neuroreport 1, 29–32.

    Article  PubMed  CAS  Google Scholar 

  33. Sucher N. J., Aizenman E., and Lipton S. A. (1991) N-methyl-D-aspartate antagonists prevent kainate neurotoxicity in rat retinal ganglion cells in vitro. J. Neurosci. 11, 966–971.

    PubMed  CAS  Google Scholar 

  34. Sucher N. J., Lipton S. A., and Dreyer E. B. (1997) Molecular basis of glutamate toxicity in retinal ganglion cells. Vision Res. 37, 3483–3493.

    Article  PubMed  CAS  Google Scholar 

  35. Mayer M. L., Westbrook G. L., and Guthrie P. B. (1984) Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309, 261–263.

    Article  PubMed  CAS  Google Scholar 

  36. Boje K. M., Skolnick P., Raber J., Fletcher R. T., and Chader G. (1992) Strychnine-insensitive glycine receptors in embryonic chick retina: characteristics and modulation of NMDA neurotoxicity. Neurochem. Int. 20, 473–486.

    Article  PubMed  CAS  Google Scholar 

  37. Johnson J. W. and Ascher P. (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325, 529–531.

    Article  PubMed  CAS  Google Scholar 

  38. Kleckner N. W. and Dingledine R. (1988) Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science 241, 835–837.

    Article  PubMed  CAS  Google Scholar 

  39. Ishii T., Moriyoshi K., Sugihara H., et al. (1993) Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. J. Biol. Chem. 268, 2836–2843.

    PubMed  CAS  Google Scholar 

  40. Kutsuwada T., Kashiwabuchi N., Mori H., et al. (1992) Molecular diversity of the NMDA receptor channel. Nature 358, 36–41.

    Article  PubMed  CAS  Google Scholar 

  41. Stevens E. R., Esguerra M., Kim P. M., et al. (2003) D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors. Proc. Natl. Acad. Sci. USA. 100, 6789–6794.

    Article  PubMed  CAS  Google Scholar 

  42. Mori H. and, Mishina M. (1995) Structure and function of the NMDA receptor channel. Neuropharmacology 34, 1219–1237.

    Article  PubMed  CAS  Google Scholar 

  43. Parsons C. G., Danysz W., Quack G., et al. (1997) Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization. J. Pharmacol. Exp. Ther. 283, 1264–1275.

    PubMed  CAS  Google Scholar 

  44. Guzikowski A. P., Cai S. X., Espitia S. A., et al. (1996) Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites. J. Med. Chem. 39, 4643–4653.

    Article  PubMed  CAS  Google Scholar 

  45. Vandenbranden C. A., Kamphuis W., Nunes Cardozo B., and Kamermans M. (2000) Expression and localization of ionotropic glutamate receptor subunits in the goldfish retina—an in situ hybridization and immunocytochemical study. J. Neurocytol. 29, 729–742.

    Article  PubMed  CAS  Google Scholar 

  46. Eliasof S. and Werblin F. (1993) Characterization of the glutamate transporter in retinal cones of the tiger salamander. J. Neurosci. 13, 402–411.

    PubMed  CAS  Google Scholar 

  47. Sarantis M., Everett K., and Attwell D. (1988) A presynaptic action of glutamate at the cone output synapse. Nature 332, 451–453.

    Article  PubMed  CAS  Google Scholar 

  48. Tachibana M. and Kaneko A. (1988) L-glutamate-induced depolarization in solitary photoreceptors: a process that may contribute to the interaction between photoreceptors in situ. Proc. Natl. Acad. Sci. USA 85, 5315–5319.

    Article  PubMed  CAS  Google Scholar 

  49. Fletcher E. L., Hack, I., Brandstätter J. H., and Wässle H. (2000) Synaptic localization of NMDA receptor subunits in the rat retina. J. Comp. Neurol. 420, 98–112.

    Article  PubMed  CAS  Google Scholar 

  50. Kalloniatis M., Sun D., Foster L., Haverkamp S., and Wässle H. (2004) Localization of NMDA receptor subunits and mapping NMDA dreive within the mammalian retina. Vis. Neurosci. 21, 587–597.

    Article  PubMed  Google Scholar 

  51. Yoshikami D. (1981) Transmitter sensitivity of neurons assayed by autoradiography. Science 212, 929–930.

    Article  PubMed  CAS  Google Scholar 

  52. Goebel D. J., Aurelia J. L., Tai Q., Jojich L., and Poosch M. S. (1998) Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina. Brain Res. 808, 141–154.

    Article  PubMed  CAS  Google Scholar 

  53. Blanco R. and de la Villa P. (1999) Ionotropic glutamate receptors in isolated horizontal cells of the rabbit retina. Eur. J. Neurosci. 11, 867–873.

    Article  PubMed  CAS  Google Scholar 

  54. Eliasof S. and Jahr C. E. (1997) Rapid AMPA receptor desensitization in catfish cone horizontal cells. Vis. Neurosci. 14, 13–18.

    PubMed  CAS  Google Scholar 

  55. Lu T., Shen Y., and Yang X. L. (1998) Desensitization of AMPA receptors on horizontal cells isolated from crucian carp retina. Neurosci. Res. 31, 123–135.

    Article  PubMed  CAS  Google Scholar 

  56. Shen Y., Zhou Y., and Yang X. L. (1999) Characterization of AMPA receptors on isolated amacrine-like cells in carp retina. Eur. J. Neurosci. 11, 4233–4240.

    Article  PubMed  CAS  Google Scholar 

  57. Shen Y., Lu T., and Yang X. L. (1999) Modulation of desensitization at glutamate receptors in isolated crucian carp horizontal cells by concavalin A, cyclothiazide, aniracetam and PEPA. Neuroscience 89, 979–990.

    Article  PubMed  CAS  Google Scholar 

  58. Yang J. H., Maple B., Gao F., Maguire G., and Wu S. M. (1998) Postsynaptic responses of horizontal cells in the tiger salamander retina are mediated by AMPA-preferring receptors. Brain Res. 797, 125–134.

    Article  PubMed  CAS  Google Scholar 

  59. Marc R. E. (1999) Mapping glutamatergic drive in the vertebrate retina with a channel-permeant organic cation. J. Comp. Neurol. 407, 47–64.

    Article  PubMed  CAS  Google Scholar 

  60. Gründer T., Kohler K., Kaletta A., and Guenther E. (2000) The distribution and developmental regulation of NMDA receptor subunit proteins in the outer and inner retina of the rat. J. Neurobiol. 44, 333–342.

    Article  PubMed  Google Scholar 

  61. Picaud S., Hicks D., Forster V., Sahel J., and Dreyfus H. (1998) Adult human retinal neurons in culture: Physiology of horizontal cells. Invest. Ophthalmol. Vis. Sci. 39, 2637–2648.

    PubMed  CAS  Google Scholar 

  62. Ariel M., Mangel S. C., and Dowling J. E. (1986) N-methyl D-aspartate acts as an antagonist of the photoreceptor transmitter in the carp retina. Brain Res. 372, 143–148.

    Article  PubMed  CAS  Google Scholar 

  63. Zhou Z. J., Fain G. L., and Dowling J. E. (1993) The excitatory and inhibitory amino acid receptors on horizontal cells isolated from the white perch retina. J. Neurophysiol. 70, 8–19.

    PubMed  CAS  Google Scholar 

  64. Harsanyi K., Wang Y., and Mangel S. C. (1996) Activation of NMDA receptors produces dopamine-mediated changes in fish retinal horizontal cell light responses. J. Neurophysiol. 75, 629–647.

    PubMed  CAS  Google Scholar 

  65. O'Dell T. J. and Christensen B. N. (1989) Horizontal cells isolated from catfish retina contain two types of excitatory amino acid receptors. J. Neurophysiol. 61, 1097–1109.

    PubMed  Google Scholar 

  66. Davis S. F. and, Linn C. L. (2003) Activation of NMDA receptors linked to modulation of voltage-gated ion channels and functional implications. Am. J. Physiol. Cell Physiol. 284, C757-C768.

    PubMed  CAS  Google Scholar 

  67. Davis S. F. and Linn C. L. (2003) Mechanism linking NMDA receptor activation to modulation of voltage-gated sodium current in distal retina. Am. J. Physiol. Cell Physiol. 284, C1193-C1204.

    PubMed  CAS  Google Scholar 

  68. Shen Y., Zhang M., Jin Y., and Yang X. L. (2006) Functional N-methyl-D-aspartate receptors are expressed in cone-driven horizontal cells in carp retina. Neurosignals 15, 174–179.

    Article  PubMed  CAS  Google Scholar 

  69. Nelson R. and Kolb H. (2003) ON and OFF pathways in the vertebrate retina and visual system. In: The Visual Neurosciences, Chalupa L. M., Werner J. S., eds., The MIT Press, Cambridge, MA, pp. 260–278.

    Google Scholar 

  70. Wässle H. (2004) Parallel processing in the mammalian retina. Nat. Rev. Neurosci. 5, 747–757.

    Article  PubMed  CAS  Google Scholar 

  71. Euler T., Schneider H., and Wässle H. (1996) Glutamate responses of bipolar cells in a slice preparation of the rat retina. J. Neurosci. 16, 2934–2944.

    PubMed  CAS  Google Scholar 

  72. Hartveit E. (1996) Membrane currents evoked by ionotropic glutamate receptor agonists in rod bipolar cells in the rat retinal slice preparation. J. Neurophysiol. 76, 401–422.

    PubMed  CAS  Google Scholar 

  73. Thoreson W. B. and Miller R. F. (1993) Membrane currents evoked by excitatory amino acid agonists in ON bipolar cells of the mud-puppy retina. J. Neurophysiol. 70, 1326–1338.

    PubMed  CAS  Google Scholar 

  74. Sasaki T. and Kaneko A. (1996) L-Glutamate-induced responses in OFF-type bipolar cells of the cat retina. Vision Res. 36, 787–795.

    Article  PubMed  CAS  Google Scholar 

  75. Grunert U., Lin B., and Martin P. R. (2003) Glutamate receptors at bipolar synapses in the inner plexiform layer of primate retina: light microscopic analysis. J. Comp. Neurol. 466, 136–147.

    Article  PubMed  CAS  Google Scholar 

  76. Brandstätter J. H., Hartveit E., Sassoe-Pognetto M., and Wässle H. (1994) Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. Eur. J. Neurosci. 6, 1100–1112.

    Article  PubMed  Google Scholar 

  77. Wenzel A., Benke D., Mohler H., and Fritschy J. M. (1997) N-methyl-D-aspartate receptors containing the NR2D subunit in the retina are selectively expressed in rod bipolar cells. Neuroscience 78, 1105–1112.

    Article  PubMed  CAS  Google Scholar 

  78. Müller F., Greferath U., Wässle H., Wisden W., and Seeburg P. (1992) Glutamate receptor expression in the rat retina. Neurosci. Lett. 138, 179–182.

    Article  PubMed  Google Scholar 

  79. Hughes T. E. (1997) Are there ionotropic glutamate receptors on the rod bipolar cell of the mouse retina?, Vis. Neurosci. 14, 103–109.

    PubMed  CAS  Google Scholar 

  80. Lo W., Molloy R., and Hughes T. E. (1998) Ionotropic glutamate receptors in the retina: moving from molecules to circuits. Vision Res. 38, 1399–1410.

    Article  PubMed  CAS  Google Scholar 

  81. Karschin A. and Wässle H. (1990) Voltage-and transmitter-gated currents in isolated rod bipolar cells of rat retina. J. Neurophysiol. 63, 860–876.

    PubMed  CAS  Google Scholar 

  82. Hartveit E. (1997) Functional organization of cone bipolar cells in the rat retina. J. Neurophysiol. 77, 1716–1730.

    PubMed  CAS  Google Scholar 

  83. MacNeil M. A. and, Masland R. H. (1998) Extreme diversity among amacrine cells: implications for function. Neuron 20, 971–982.

    Article  PubMed  CAS  Google Scholar 

  84. MacNeil M. A., Heussy J. K., Dacheux R. F., Raviola E., and Masland R. H. (1999) The shapes and numbers of amacrine cells: matching of photofilled with Golgi-stained cells in the rabbit retina and comparison with other mammalian species. J. Comp. Neurol. 413, 305–326.

    Article  PubMed  CAS  Google Scholar 

  85. Masland R. H. (2001) The fundamental plan of the retina. Nat. Neurosci. 4, 877–886.

    Article  PubMed  CAS  Google Scholar 

  86. Slaughter M. M. and Miller R. F. (1983) The role of excitatory amino acid transmitters in the mudpuppy retina: an analysis with kainic acid and N-methyl aspartate. J. Neurosci. 3, 1701–1711.

    PubMed  CAS  Google Scholar 

  87. Massey S. C. and Miller R. F. (1990) N-methyl-D-aspartate receptors of ganglion cells in rabbit retina. J. Neurophysiol. 63, 16–30.

    PubMed  CAS  Google Scholar 

  88. Dixon D. B. and Copenhagen D. R. (1992) Two types of glutamate receptors differentially excite amacrine cells in the tiger salamander retina. J. Physiol. 449, 589–606.

    PubMed  CAS  Google Scholar 

  89. Coleman P. A. and Miller R. F. (1988) Do N-methyl-D-aspartate receptors mediate synaptic responses in the mudpuppy retina? J. Neurosci. 8, 4728–4733.

    PubMed  CAS  Google Scholar 

  90. Lukasiewicz P. D. and McReynolds J. S. (1985) Synaptic transmission at N-methyl-D-aspartate receptors in the proximal retina of the mudpuppy. J. Physiol. 367, 99–115.

    PubMed  CAS  Google Scholar 

  91. Tran M. N., Higgs M. H., and Lukasiewicz P. D. (1999) AMPA receptor kinetics limit retinal amacrine cell excitatory synaptic responses. Vis. Neurosci. 16, 835–842.

    Article  PubMed  CAS  Google Scholar 

  92. Ferreira I. L., Duarte C. B., Santos P. F., Carvalho C. M., and Carvalho A. P. (1994) Release of [3H]GABA evoked by glutamate receptor agonists in cultured chick retina cells: effect of Ca2+. Brain Res. 664, 252–256.

    Article  PubMed  CAS  Google Scholar 

  93. Huba R. and Hofmann H. D. (1991) Transmitter-gated currents of GABAergic amacrine-like cells in chick retinal cultures. Vis. Neurosci. 6, 303–314.

    PubMed  CAS  Google Scholar 

  94. Ientile R., Pedale S., Picciurro V., Macaione V., Fabiano C., and Macaione S. (1997) Nitric oxide mediates NMDA-evoked [3H]GABA release from chick retina cells. FEBS Lett. 417, 345–348.

    Article  PubMed  CAS  Google Scholar 

  95. Kubrusly R. C., de Mello M. C., and de Mello F. G. (1998) Aspartate as a selective NMDA receptor agonist in cultured cells from the avian retina. Neurochem. Int. 32, 47–52.

    Article  PubMed  CAS  Google Scholar 

  96. Yamashita M., Huba R., and Hofmann H. D. (1994) Early in vitro development of voltage-and transmitter-gated currents in GABAergic amacrine cells. Brain Res. Dev. Brain Res. 82, 95–102.

    Article  PubMed  CAS  Google Scholar 

  97. Boos R., Schneider H., and Wässle H. (1993) Voltage-and transmitter-gated currents of AII-amacrine cells in a slice preparation of the rat retina. J. Neurosci. 13, 2874–2888.

    PubMed  CAS  Google Scholar 

  98. Hartveit E. and Veruki M. L. (1997) AII amacrine cells express functional NMDA receptors. Neuroreport 8, 1219–1223.

    Article  PubMed  CAS  Google Scholar 

  99. Hartveit E. (1999) Reciprocal synaptic interactions between rod bipolar cells and amacrine cells in the rat retina. J. Neurophysiol. 81, 2923–2936.

    PubMed  CAS  Google Scholar 

  100. Hartveit, E., Brandstätter, J. H., Sassoe-Pognetto M., Laurie D. J., Seeburg P. H., and Wässle H. (1994) Localization and developmental expresion of the NMDA receptor subunit NR2A in the mammalian retina. J. Comp. Neurol. 348, 570–582.

    Article  PubMed  CAS  Google Scholar 

  101. Brandstätter J. H., Koulen P., and Wässle H. (1998) Diversity of glutamate receptors in the mammalian retina. Vision Res. 38, 1385–1397.

    Article  PubMed  Google Scholar 

  102. Mittman, S., Taylor W. R., and Copenhagen D. R. (1998) Concomitant activation of two types of glutamate receptor mediates excitation of salamander retinal ganglion cells. J. Physiol. 428, 175–197.

    Google Scholar 

  103. Zhou Z. J., Marshak D. W., and Fain G. L. (1994) Amino acid receptors of midget and parasol ganglion cells in primate retina. Proc. Natl. Acad. Sci. USA, 91, 4907–4911.

    Article  PubMed  CAS  Google Scholar 

  104. Cohen E. D. and Miller R. F. (1994) The role of NMDA and non-NMDA excitatory amino acid receptors in the functional organization of primate retinal ganglion cells Vis. Neurosci. 11, 317–332.

    PubMed  CAS  Google Scholar 

  105. Hensley S. H., Yang X. L., and Wu S. M. (1993) Identification of glutamate receptor subtypes mediating inputs to bipolar cells and ganglion cells in the tiger salamander retina. J. Neurophysiol. 69, 2099–2107.

    PubMed  CAS  Google Scholar 

  106. Diamond J. S. and, Copenhagen D. R. (1993) The contribution of NMDA and non-NMDA receptors to the light-evoked input-output characteristics of retinal ganglion cells. Neuron 11, 725–738.

    Article  PubMed  CAS  Google Scholar 

  107. Yu W., and Miller R. F. (1996) The mechanism by which NBQX enhances NMDA currents in retinal ganglion cells. Brain Res. 709, 184–196.

    Article  PubMed  CAS  Google Scholar 

  108. Cohen E. D. and Miller R. F. (1995) Quinoxalines block the mechanism of directional selectivity in ganglion cells of the rabbit retina. Proc. Natl. Acad. Sci. USA 92, 1127–1131.

    Article  PubMed  CAS  Google Scholar 

  109. Kittila C.A. and Massey S. C. (1997) Pharmacology of directionally selective ganglion cells in the rabbit retina. J. Neurophysiol. 77, 675–689.

    PubMed  CAS  Google Scholar 

  110. Gottesman J. and Miller R.F. (2003) N-methyl-D-aspartate receptors contribute to the baseline noise of retinal ganglion cells. Vis. Neurosci. 20, 329–333.

    PubMed  Google Scholar 

  111. Lukasiewicz P. D. and Roeder R. C. (1995) Evidence for glycine modulation of excitatory synaptic inputs to retinal ganglion cells. J. Neurosci. 15, 4592–4601.

    PubMed  CAS  Google Scholar 

  112. Baranano D. E., Ferris C. D., and Snyder S. H. (2001) Atypical neural messengers Trends Neurosci. 24, 99–106

    Article  PubMed  CAS  Google Scholar 

  113. O'Brien K. B., Esguerra M., Klug C. T., Miller R. F., and Bowser M. T. (2003) A high-through-put on-line microdialysis-capillary assay for D-serine. Electrophoresis 24, 1227–1235.

    Article  PubMed  Google Scholar 

  114. Chen S. and Diamond J. S. (2002) Synaptically released glutamate activates extrasynaptic NMDA receptors on cells in the ganglion cell layer of rat retina. J. Neurosci. 22, 2165–2173.

    PubMed  CAS  Google Scholar 

  115. Higgs M. H. and Lukasiewicz P. D. (1999) Glutamate uptake limits synaptic excitation of retinal ganglion cells. J. Neurosci. 19, 3691–3700.

    PubMed  CAS  Google Scholar 

  116. Matsui K., Hosoi N., and Tachibana M. (1998) Excitatory synaptic transmission in the inner retina: paired recordings of bipolar cells and neurons of the ganglion cell layer. J. Neurosci. 18, 4500–4510.

    PubMed  CAS  Google Scholar 

  117. Taylor W. R., Chen E., and Copenhagen D. R. (1995) Characterization of spontaneous excitatory synaptic currents in salamander retinal ganglion cells. J. Physiol. 486 (Pt 1), 207–221

    PubMed  CAS  Google Scholar 

  118. Taschenberger H., Engert F., and Grantyn R. (1995) Synaptic current kinetics in a solely AMPA-receptor-operated glutamatergic synapse formed by rat retinal ganglion neurons. J. Neurophysiol. 74, 1123–1136.

    PubMed  CAS  Google Scholar 

  119. Tian N., Hwang T. N., and Copenhagen D.R. (1998) Analysis of excitatory and inhibitory spontaneous synaptic activity in mouse retinal ganglion cells J. Neurophysiol., 80, 1327–1340.

    PubMed  CAS  Google Scholar 

  120. Matsui K., Hasegawa J., and Tachibana M. (2001) Modulation of excitatory synaptic transmission by GABA(C) receptor-mediated feedback in the mouse inner retina. J Neurophysiol. 86, 2285–2298.

    PubMed  CAS  Google Scholar 

  121. Vigh J. and Gersdorff H. (2005) Prolonged reciprocal signaling via NMDA and GABA receptors at a retinal ribbon synapse. J. Neurosci. 25, 11,412–11,423.

    Article  CAS  Google Scholar 

  122. Kim T. W., Kang K. B., Choung H. K., Park K. H., and Kim, D. M. (2000) Elevated glutamate levels in the vitreous body of an in vivo model of optic nerve ischemia. Arch. Ophthalmol. 118, 533–536.

    PubMed  CAS  Google Scholar 

  123. Neal M. J., Cunningham J. R., Hutson, P. H., and Hogg J. (1994) Effects of ischaemia on neurotransmitter release from the isolated retina. J. Neurochem. 62, 1025–1033.

    Article  PubMed  CAS  Google Scholar 

  124. Quigley H. A. (1999) Neuronal death in glaucoma. Prog. Retin. Eye Res. 18, 39–57.

    Article  PubMed  CAS  Google Scholar 

  125. Osborne N. N., Safa R., and Nash M. S. (1999) Photoreceptors are preferentially affected in the rat retina following permanent occlusion of the carotid arteries. Vision Res. 39, 3995–4002.

    Article  PubMed  CAS  Google Scholar 

  126. Lam T. T., Abler A. S., Kwong J. M., Tso M. O. (1999) N-methyl-D-aspartate (NMDA)-induced apoptosis in rat retina. Invest. Ophthalmol. Vis. Sci. 40, 2391–2397.

    PubMed  CAS  Google Scholar 

  127. Vorwerk C. K., Kreutz M. R., Dreyer E. B., and Sebel B. A. (1996) Systemic L-kynurenine administration partially protects against NMDA, but not kainate-induced degeneration of retinal ganglion cells, and reduces visual discrimination deficits in adult rats. Invest. Ophthalmol. Vis. Sci. 37, 2382–2392.

    PubMed  CAS  Google Scholar 

  128. Dreyer E. B., Zhang D., Lipton S. A. (1995) Transcriptional of translation inhibition blocks low dose NMDA-mediated cell death. Neuroreport 6, 942–944.

    PubMed  CAS  Google Scholar 

  129. Schumer R. A. and Podos S. M. (1994) The nerve of glaucoma. Arch. Ophthalmol. 112, 37–44.

    PubMed  CAS  Google Scholar 

  130. Hahn J. S., Aizenman E., and Lipton S. A. (1988) Central mammalian neurons normally resistant to glutamate toxicity are made sensitive by elevated extracellular Ca2+: toxicity is blocked by the N-methyl-D-aspartate antagonist MK-801. Proc. Natl. Acad. Sci. USA. 85, 6556–6560.

    Article  PubMed  CAS  Google Scholar 

  131. Mosinger J. L., Price M. T., Bai H. Y., Xiao H., Wozniak D. F., and Oney J. W. (1991) Blockade of both NMDA and non-NMDA receptors is required for optimal protection against ischemic neuronal degeneration in the in vivo adult mammalian retina. Exp. Neurol. 113, 10–17.

    Article  PubMed  CAS  Google Scholar 

  132. Otori Y., Wei J. Y., and Barnstable C. J. (1998) Neurotoxic effects of low doses of glutamate on purified rat retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 39, 972–981.

    PubMed  CAS  Google Scholar 

  133. Osborne N. N. and Herrera A. J. (1994) The effect of experimental ischaemia and excitatory amino acid agonists on the GABA and serotonin immunoreactivities in the rabbit retina. Neuroscience 59, 1071–1081.

    Article  PubMed  CAS  Google Scholar 

  134. Lombardi G., Moroni F., and Moroni F. (1994) Glutamate receptor antagonists protect against ischemia-induced retinal damage. Eur. J. Pharmacol. 271, 489–495.

    Article  PubMed  CAS  Google Scholar 

  135. Ullian E. M., Barkis W. B., Chen, S., Diamond J. S., and Barres B. A. (2004) Invulnerability of retinal ganglion cells to NMDA excitotoxicity. Mol. Cell Neurosci. 26, 544–557.

    Article  PubMed  CAS  Google Scholar 

  136. Manabe, S., Gu Z., Lipton S. A., (2005) Activation of matrix metalloproteinase-9 via neuronal nitric oxide synthase contributes to NMDA-induced retinal ganglion cell death. Invest. Ophthalmol. Vis. Sci. 46, 4747–4753.

    Article  PubMed  Google Scholar 

  137. Chang C. and Werb Z. (2001) The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 11, S37-S43.

    PubMed  CAS  Google Scholar 

  138. Lipton S. A., Choi Y. B., Pan Z. H., et al (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364, 626–632.

    Article  PubMed  CAS  Google Scholar 

  139. Narumiya S., Ishizaki T. and Watanabe N. (1997) Rho effectors and reorganization of actin cytoskeleton. FEBS Lett. 410, 68–72.

    Article  PubMed  CAS  Google Scholar 

  140. Kitaoka Y., Kitaoka Y., Kumai T., et al. (2004) Involvement of RhoA and possible neuroprotective effect of fasudil, a Rho kinase inhibitor, in NMDA-induced neurotoxicity in the rat retina. Brain Res. 1018, 111–118.

    Article  PubMed  CAS  Google Scholar 

  141. Lam T. T., Siew E., Chu R., and Tso M. O. (1997) Ameliorative effect of MK-801 on retinal ischemia. J. Ocul. Pharmacol. Ther. 13, 129–137.

    PubMed  CAS  Google Scholar 

  142. Osborne N. N. (1999) Memantine reduces alterations to the mammalian retina, in situ, induced by ischemia. Vis. Neurosci. 16, 45–52.

    Article  PubMed  CAS  Google Scholar 

  143. Osborne N. N., Schwarz M., and Pergande G. (1996) Protection of rabbit retina from ischemic injury by flupirtine. Invest. Ophthalmol. Vis. Sci. 37, 274–280.

    PubMed  CAS  Google Scholar 

  144. Qian A., Buller A. L., and Johnson J. W. (2005) NR2 subunit-dependence of NMDA receptor channel block by external Mg2+. J. Physiol. 562, 319–331.

    Article  PubMed  CAS  Google Scholar 

  145. Masu M., Iwakabe H., Tagawa Y., et al. (1995) Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80, 757–765.

    Article  PubMed  CAS  Google Scholar 

  146. Perkins B. D., Nicholas C. S., Baye L. M., Link B. A., and Dowling J. E. (2005) dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina. Dev. Dyn. 233, 680–694.

    Article  PubMed  CAS  Google Scholar 

  147. Du J. L., Yang X. L. (2000) Subcellular localization and complements of GABAA and GABA(C) receptors on bullfrog retinal bipolar cells. J. Neurophysiol. 84, 666–676.

    PubMed  CAS  Google Scholar 

  148. Shen W. and Slaughter M. M. (2001) Multireceptor GABA ergic regulation of synaptic communication in amphibian retina. J. Physiol. 530, 55–67.

    Article  PubMed  CAS  Google Scholar 

  149. Tachibana M. and Kaneko A. (1988) Retinal bipolar cells receive negative feedback input from GABAergic amacrine cells. Vis. Neurosci. 1, 297–305.

    Article  PubMed  CAS  Google Scholar 

  150. Watanabe M., Mishina M., and Inoue Y. (1994) Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina. Brain Res. 634, 328–332.

    Article  PubMed  CAS  Google Scholar 

  151. Wong R. O. (1995) Effects of glutamate and its analogs on intracellular calcium levels in the developing retina. Vis. Neurosci. 12, 907–917.

    Article  PubMed  CAS  Google Scholar 

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Shen, Y., Liu, XL. & Yang, XL. N-Methyl-d-aspartate receptors in the retina. Mol Neurobiol 34, 163–179 (2006). https://doi.org/10.1385/MN:34:3:163

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