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Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA

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Abstract

Conditions causing a reduction of oxygen availability (anoxia), such as stroke or diabetes, result in drastic changes in ion movements, levels of neurotransmitters and metabolites and subsequent neural death. Currently, there is no clinically available treatment for anoxia induced neural cell death resulting in drastic and permanent central nervous system dysfunction. However, there have been some exciting developments in experimentally induced anoxic conditions where several classes of drugs appear to significantly reduce neural cell death. This report aims to provide the foundations for understanding both the basic mechanisms involved in retinal ischaemic damage and experimental treatments used to prevent such damage. We discuss the normal release, actions and uptake of the fast retinal neurotransmitters, glutamate and GABA, in the vertebrate retina. Immunocytochemistry is used to demonstrate that both glutamate and GABA are found in the macaque retina. Following this is a discussion on how ischaemia may enhance neurotransmitter release or disrupt its uptake, thus causing an increase in extracellular concentration of these neurotransmitters and subsequent neuronal damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because excess glutamate is the likely cause of retinal ischaemic damage. Finally, the mechanisms behind four possible modes of treatment of neurotransmitter toxicity and their advantages and disadvantages are discussed. Hopefully, further research in this area will lead to the development of a rational therapy for retinal, as well as cerebral ischaemia.

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Abbreviations

α-KG:

α-ketoglutarate

AAT:

aspartate amino transferase

AC:

amacrine cell

ACL:

amacrine cell layer

BC:

bipolar cell

CNS:

central nervous system

EAA:

excitatory amino acids

G'ase:

glutaminase

GABA:

γ-amino butyric acid

GABA-T:

GABA transaminase

GAD:

glumatic acid decarboxylase

GC:

ganglion cell

GCL:

ganglion cell layer

GDH:

glutamate dehydrogenase

gj:

gap junction

GS:

glutamine synthetase

HC:

horizontal cell

ILM:

inner limiting membrane

INL:

inner nuclear layer

IPC:

inter-plexiform cell

IPL:

inner plexiform layer

IS:

inner segment of photoreceptor

NFL:

nerve fibre layer

NMDA:

N-methyl-D-aspartate

OLM:

outer limiting membrane

ONL:

outer nuclear layer

OPL:

outer plexiform layer

OS:

outer segment of photoreceptor

Ox:

acetateoxaloacetate

RL:

receptor layer

SSAD:

succinate semi-aldehyde decarboxylase

Succinate SA:

succinate semi aldehyde

TCA cycle:

tricarboxylic acid cycle

References

  1. Ames III A, Gurian BS. Effects of glucose and oxygen deprivation on function of isolated mammalian retina, J Neurophys 1963; 26: 617–34.

    Google Scholar 

  2. Dowling JE. The retina: An approachable part of the brain. Cambridge, MA: The Belknap Press, 1987.

    Google Scholar 

  3. Werblin F. Synaptic connections, receptive fields and patterns of activity in the tiger salamander retina, Inv Ophthalmol Vis Sci 1991; 32: 459–88.

    Google Scholar 

  4. Ripps H, Witkovsky P. Neuron-glia interaction in the brain and retina. In: Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 4. Oxford: Pergamon Press, 1985: 181–219.

    Google Scholar 

  5. Famiglietti EV Jr, Kolb H. Structural basis of ‘on’ and ‘off’±center responses in retinal ganglion cells, Science 1976; 194: 193–5.

    Google Scholar 

  6. Famiglietti EV Jr, Kaneko A, Tachibana M. Neuronal architecture of on and off pathways to ganglion cells in carp retina, Science 1977; 195: 1267–9.

    Google Scholar 

  7. Nelson R, Kolb H. Synaptic patterns and response properties of bipolar and ganglion cells in the cat retina, Vision Res 1983; 23: 1183–95.

    Google Scholar 

  8. Dacheux RF, Raviola E. The rod pathway in the rabbit retina: a depolarizing bipolar and amacrine cell, J Neurosci 1986; 6: 331–45.

    Google Scholar 

  9. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular biology of the cell, 2nd ed. New York: Garland Publishing Inc, 1989: ch 19, 1059–136.

    Google Scholar 

  10. Iversen LL. Amino acids and peptides: fast and slow chemical signals in the nervous system? Proc R Soc Lond B 1984; 221: 245–60.

    Google Scholar 

  11. Massey S. Cell types using glutamate as a neurotransmitter in the vertebrate retina. In: Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 9. Oxford: Pergamon Press, 1990: 399–425.

    Google Scholar 

  12. Marc RE. The role of glycine in the mammalian retina. In: Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 8. Oxford: Pergamon Press, 1989: 67–107.

    Google Scholar 

  13. Morgan IG. Kainic acid as a tool in retinal research. In: Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 2. Oxford: Pergamon Press, 1983: 249–66.

    Google Scholar 

  14. Massey SC, Redburn PA. Transmitter circuits in the vertebrate retina, Prog Neurobiol 1987; 28: 55–96.

    Google Scholar 

  15. Yazulla S. GABAergic mechanisms in the retina. In: Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 5. Oxford: Pergamon Press, 1986; 1–51.

    Google Scholar 

  16. Stell WK. Putative peptide transmitters, amacrine cell diversity and function in the inner plexiform layer. In: Gallego A, Gouras P, eds. Neurocircuitry of the retina. A Cajal memorial. New York: Elsevier, 1985: 171–87.

    Google Scholar 

  17. Ehinger B. Functional role of dopamine in the retina. In: Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 2, Oxford: Pergamon Press, 1983: 213–32.

    Google Scholar 

  18. Zalutsky RA, Miller RF. The physiology of somatostatin in the rabbit retina, J Neurosci 1990; 10: 383–93.

    Google Scholar 

  19. Zalutsky RA, Miller RF. The physiology of substance P in the rabbit retina, J Neurosci 1990; 10: 394–402.

    Google Scholar 

  20. Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues, Proc Nat Acad Sci USA 1991; 88: 7797–801.

    Google Scholar 

  21. Hope BT, Michael GJ, Knigge KM, Vincent SR. Neuronal NADPH diaphorase is a nitric oxide synthase, Proc Nat Acad Sci USA 1991; 88: 2811–4.

    Google Scholar 

  22. Marc RE, Liu W-L, Kalloniatis M, Raiguel SF, Van Haesendonck E. Patterns of glutamate immunoreactivity in the goldfish retina, J Neurosci 1990; 10: 4006–34.

    Google Scholar 

  23. Marc RE, Massey SC, Kalloniatis M, Basinger SF. Immunochemical evidence that the fast neurotransmitter of rods, cones, bipolar and ganglion cells is glutamic acid, Inv Ophthalmol Vis Sci (suppl.) 1989; 30: 320.

    Google Scholar 

  24. Ehinger B. Glutamate as a retinal neurotransmitter, In: Weiler R, Osborne NN, eds. Neurobiology of the inner retina. Berlin: Springer Verlag; 1989: 1–14.

    Google Scholar 

  25. Kolb H, Nelson R. Functional neurocircuitry of amacrine cells in the cat. In: Gallego A, Gouras P, eds. Neurocircuitry of the retina. A Cajal memorial. New York: Elsevier, 1985: 215–32.

    Google Scholar 

  26. Kolb H, Nelson R. Neural architecture in the cat retina. In Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 3. Oxford: Pergamon Press, 1984: 21–60.

    Google Scholar 

  27. Marc RE. The role of glycine in retinal circuitry. In: WW Morgan, ed. Retinal transmitters and modulators: models for the brain, Vol 1. Boca Raton, Fl: CRC Press, 1985: 199–58.

    Google Scholar 

  28. Kalloniatis M, Marc RE. Interplexiform cells of the goldfish retina, J Comp Neurol 1990; 297: 340–58.

    Google Scholar 

  29. Ball A. Immunocytochemical and autoradiographic localization of GABAergic neurons in the goldfish retina, J Comp Neurol 1987; 255: 317–25.

    Google Scholar 

  30. Marc RE. The anatomy of multiple GABAergic and glycinergic pathways in the inner plexiform layer of the goldfish retina. In: Weiler R, Osborne NN, eds. Neurobiology of the inner retina. Berlin: Springer Verlag, 1989: 53–64.

    Google Scholar 

  31. Marc RE. Neurochemical stratification in the inner plexiform layer of the vertebrate retina, Vis Res 1986; 26: 223–38.

    Google Scholar 

  32. Grünert U, Wassle H. GABA-like immunoreactivity in the Macaque monkey retina: A light and electron microscopic study, J Comp Neurol 1990; 297: 509–24.

    Google Scholar 

  33. Wassle H, Chun MH. GABA-like immunoreactivity in the cat retina: Light microscopy, J Comp Neurol 1989; 279: 43–54.

    Google Scholar 

  34. Stockton RA, Slaughter MM. Depolarizing actions of GABA and glycine on Amphibian retinal horizontal cells, J Neurophys 1991; 65: 680–92.

    Google Scholar 

  35. Voaden MJ, Lake N, Nathwani B. A comparison of γ-aminobutyric acid metabolism in neurones versus glial cells using intact isolated retinae, J Neurochem 1977; 28: 457–9.

    Google Scholar 

  36. Voaden MJ, Marshall J, Murani N. The uptake of [3H] γ-aminobutyric acid and [3H] glycine by the isolated retina of the frog, Brain Res 1974; 67: 115–32.

    Google Scholar 

  37. Voaden MJ. Gamma-aminobutyric acid and glycine as retinal neurotransmitters. In: Bonting SL, ed. Transmitters in the visual process. Oxford: Pergamon Press, 1976: 107–25.

    Google Scholar 

  38. Voaden MJ. The localization and metabolism of neuroactive amino acids in the retina. In: Fonnum F, ed. Amino acids as chemical transmitters. New York: Plenum Press, 1978: 257–74.

    Google Scholar 

  39. Ehinger B. Glial and neuronal uptake of GABA, glutamic acid, glutamine and glutathione in the rabbit retina, Exp Eye Res 1977; 25: 221–34.

    Google Scholar 

  40. Mosinger JL, Yazulla S, Studholme KM. GABA-like immunoreactivity in the vertebrate retina: A species comparison, Exp Eye Res 1986; 42: 631–44.

    Google Scholar 

  41. Werman R. A review — criteria for indentification of a central nervous transmitter, Comp Biochem Physiol 1966; 18: 745–66.

    Google Scholar 

  42. Caruso DM, Owczarzak MT, Goebel Dj, Hazlett JC, Pourcho RG. GABA-immunoreactivity in ganglion cells of the rat retina, Brain Res 1989; 476: 129–34.

    Google Scholar 

  43. Yu BC-Y, Watt CB, Lam DMK, Fry KR. GABAergic ganglion cells in the rabbit retina, Brain Res 1988; 439: 376–82.

    Google Scholar 

  44. Fredericks JM, Rayborn ME, Hollyfield JG. Glycinergic neurons in the human retina, J Comp Neurol 1984; 227: 159–72.

    Google Scholar 

  45. Marc RE, Liu S W-L. (3H) glycine-accumulating neurons of the human retina, J Comp Neurol 1985; 232: 241–60.

    Google Scholar 

  46. Hendrickson AE, Koontz MA, Pourcho RG, Sarthy PV, Goebel DJ. Localization of glycine-containing neurons in the Macaca monkey retina, J Comp Neurol 1988; 273: 473–87.

    Google Scholar 

  47. Daly EC, Aprison MH. Distribution of serine hydroxymethyltransferase and glycine transaminase in several areas of the central nervous system of the rat, J Neurochem 1974; 22: 877–85.

    Google Scholar 

  48. Dasgupta P, Narayanaswani A. Serine transhydroxymethylase activity in vertebrate retina, J Neurochem 1982; 39: 743–6.

    Google Scholar 

  49. Bruun A, Ehinger B. Uptake of the putative neurotransmitter glycine into the rabbit retina, Inv Ophthalmol Vis Sci 1972; 11: 191–8.

    Google Scholar 

  50. Miller AM and Schwartz EA. Evidence for the indentification of synaptic transmitters released by photoreceptors of the toad retina, J Physiol 1983; 334: 325–49.

    Google Scholar 

  51. Redburn DA. Uptake and release of [14C]-GABA from rabbit retina synaptasomes, Exp Eye Res 1977; 25: 265–75.

    Google Scholar 

  52. Schwartz EA. Depolarization without calcium can release γ-aminobutyric acid from a retinal neuron, Science 1987; 238: 350–5.

    Google Scholar 

  53. Maycox PR, Peckwerth T, Hell JW, Jahn R. Glutamate uptake by brain synaptic vesicles, J Biol Chem 1988; 263: 15423–8.

    Google Scholar 

  54. Kish PE, Fischer-Bovenkerk C, Udea T. Active transport of γ-minobutyric acid and glycine into synaptic vesicles, Proc Nat Acad Sci USA 1989; 86: 3877–81.

    Google Scholar 

  55. Sladeczek F, Recasens M, Bockaert J. A new mechanism for glutamate receptor action: Phosphoinositide hydrolysis, Trends Neurosci 1988; 11: 545–9.

    Google Scholar 

  56. Miller RF and Slaughter MM. Excitatory amino acid receptors of the retina: Diversity of subtypes and conductance mechanisms. Trends Neurosci 1986; 9: 211–8.

    Google Scholar 

  57. Monaghan DT, Bridges RJ and Cotman CW. The excitatory amino acid receptors: Their classes, pharmacology and distinct properties in the function of the central nervous system, Ann Rev Pharmacol and Toxicol 1989; 29: 365–402.

    Google Scholar 

  58. Bowery NG. Classification of GABA receptors. In: Enna SJ, ed. The GABA receptors. New Jersey: Humana Press, 1984: 177–213.

    Google Scholar 

  59. Enna SJ. GABA receptors. In: Enna SJ, ed. The GABA receptors. New Jersey: Humana Press, 1984: 1–23.

    Google Scholar 

  60. Bormann J. Electrophysiology of GABAA and GABAB receptor subtypes, Trends Neurosci 1988; 11: 112–16.

    Google Scholar 

  61. Bruun A and Ehinger B. Uptake of certain possible neurotransmitters into retinal neurons of some mammals, Exp Eye Res 1974; 19: 707–10.

    Google Scholar 

  62. Marc RE, Lam DMK. Uptake of aspartic and glutamic acid by photoreceptors in goldfish retina. Proc Nat Acad Sci USA 1981; 78: 7185–89.

    Google Scholar 

  63. Barbour B, Brew H, Attwell D. Electrogenic glutamate uptake in glial cells is activated by intracellular potassium, Nature 1988; 335: 433–5.

    Google Scholar 

  64. Sarantis M, Attwell D. Glutamate uptake in mammalian retinal glia is voltage- and potassium-dependent, Brain Res 1990; 516: 322–5.

    Google Scholar 

  65. Hertz L. Functional interactions between neurons and astrocytes, I: Turn over and metabolism of putative amino acid transmitters, Prog Neurobiol 1979; 13: 277–323.

    Google Scholar 

  66. Brew H and Attwell D. Electrogenic glutamate uptake is a major current carrier in the membrane of axcolotl glial cells, Nature 1987; 327: 707–709.

    Google Scholar 

  67. Cho Y and Bannai S. Uptake of glutamate and crystine in C-6 glioma cells and in cultured astrocytes, J. Neurosci 1990; 55: 2091–7.

    Google Scholar 

  68. Mitchell CK, Redburn DA. AP4 inhibits chloride-dependent binding and uptake of [3H] glutamate in rabbit retina, Brain Res 1988; 459: 298–311.

    Google Scholar 

  69. Hampton CK, Redburn DA. Autoradiographic analysis of 3H-glutamate, 3H-dopamine and 3H-GABA accumulation in rabbit retina after kainic acid treatment, J Neurosci Res 1983; 9: 239–51.

    Google Scholar 

  70. Altschuler RA, Mosinger JL, Harmison GG, Parakkal MH, Wenthold RJ. Aspartate aminotransferase-like immunoreactivity as a marker for aspartate/glutamate in guinea pig photoreceptors, Nature 1982; 298: 657–9.

    Google Scholar 

  71. Sarthy PV, Hendrickson AE, Wu JY. L-glutamate: a neurotransmitter candidate for cone photoreceptors in the monkey retina, J Neurosci 1986; 6: 637–43.

    Google Scholar 

  72. Moscona AA. On glutamine synthetase, carbonic anhydrase and Muller glia in the retina. In: Osborne NN, Chader GJ, eds. Progress in retinal research, Vol 2. Oxford: Pergamon Press, 1983: 111–35.

    Google Scholar 

  73. Lewis GP, Erickson PA, Kaska DB, Fisher SK. Immunocytochemical comparison of Muller cells and astrocytes in the cat retina, Exp Eye Res 1988; 47: 839–53.

    Google Scholar 

  74. Yoneda Y, Roberts E, Dietz GW. A new synaptosomal biosynthetic pathway of glutamate and GABA from ornithine and its negative feedback inhibition by GABA, J Neurochem 1982; 38: 1686–94.

    Google Scholar 

  75. White RD, Neal MJ. The uptake of L-glutamate by the retina, Brain Res 1976; 111: 79–93.

    Google Scholar 

  76. Ehinger B, Ottersen OP, Storm-Mathisen J, Dowling JE. Bipolar cells in the turtle retina are strongly immunoreactive for glutamate, Proc Nat Acad Sci USA 1988; 85: 8321–5.

    Google Scholar 

  77. De Barry J, Vincendon G, Gombos G. Uptake and metabolism of L-[3H] glutamate and L-[3H] glutamine in adult rat cerebellar slices, Neurochem Res 1983; 8: 1321–35.

    Google Scholar 

  78. Marshall J, Voaden MJ. An investigation of the cells incorporating [3H] GABA and [3H] glycine in the isolated retina of the rat, Exp Eye Res 1974; 18: 367–70.

    Google Scholar 

  79. McGeer PL, Hattori T, McGeer EG. Chemical and autoradiographic analysis of γ- aminobutyric acid transport in Purkinje cells of the cerebellum, Exp Neurol 1975; 47: 26–41.

    Google Scholar 

  80. Moore CL, Gruberg ER. The distribution of succinic semialdehyde dehydrogenase in the brain and retina of the tiger salamander (Ambystoma tigrinum), Brain Res 1974; 67: 479–88.

    Google Scholar 

  81. Hyde JC, Robinson N. Localization of sites of GABA catabolism in the rat retina, Nature 1974; 248: 432–3.

    Google Scholar 

  82. Salganicoff L, De Robertis E. Subcellular distribution of glutamic decarboxylase and gamma-aminobutyric alpha-ketoglutaric transaminase, Life Sci 1963; 2: 85–91.

    Google Scholar 

  83. Balazs R, Dahl D, Harwood JR. Subcellular distribution of enzymes of glutamate metabolism in rat brain, J Neurochem 1966; 13: 897–905.

    Google Scholar 

  84. Storm-Mathisen J. High affinity uptake of GABA in presumed GABA-ergic nerve endings in rat brain, Brain Res 1975; 84: 409–27.

    Google Scholar 

  85. Bradford HF, Ward HK, Thomas AJ. Glutamate as a substrate for nerve endings, J Neurochem 1978; 30: 1453–9.

    Google Scholar 

  86. Hamberger A, Chiang G, Nylen ES, Scheff SW, Cotman CW. Stimulus evoked increase in the biosynthesis of the putative neurotransmitter glutamate in the hippocampus, Brain Res 1978; 143: 549–55.

    Google Scholar 

  87. Rosenberg PA, Aizenman E. Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of rat cerebral cortex, Neurosci Lett 1989; 103: 162–8.

    Google Scholar 

  88. Kuffler SW, Nicholls JG, Martin AR. From neuron to brain, 2nd ed. Sunderland: Sinauer Assoc Inc Publishers, 1984: ch 13, 323–60.

    Google Scholar 

  89. Newman EA. Regulation of potassium levels by glial cells in the retina, Trends Neurosci 1985; 8: 1–4.

    Google Scholar 

  90. Pentreth VW. Potassium signalling of metabolic interactions between neurons and glial cells, Trends Neurosci 1982; 5: 339–45.

    Google Scholar 

  91. Bender DA. Amino acid metabolism. Chichester: John Wiley & Sons, 1985.

    Google Scholar 

  92. David P, Lusky M, Teichberg VI. Involvement of excitatory neurotransmitters in the damage produced in chick embryo retinas by anoxia and extracellular high potassium, Exp Eye Res 1988; 46: 657–62.

    Google Scholar 

  93. Benveniste H, Drejer J, Schousboe A, Diemer NH. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischaemia monitored by intracerebral microdialysis, J Neurochem 1984; 43: 1369–74.

    Google Scholar 

  94. Simpson Jr RK, Robertson CS, Goodman JC. Spinal cord ischaemia-induced elevation of amino acids: extracellular measurement with microdialysis, Neurochem Res 1990; 15: 635–9.

    Google Scholar 

  95. Wieloch T. Endogenous excitotoxins as possible mediators of ischaemic and hypoglycemic brain damage. Advances in experimental and medical biology. In: Schwartz R, Ben-ari Y, eds. Excitatory amino acids, Vol 203. New York: Plenum, 1986: 127–38.

    Google Scholar 

  96. Wieloch T, Lindvall O, Blomqvist P, Gage FH. Evidence for amelioration of ischaemic neuronal damage in the hippocampal formation by lesions of the perforant path, Neurol Res 1985; 7: 24–9.

    Google Scholar 

  97. Rothman SM. Synaptic activity mediates death of hypoxic neurons, Science 1983; 220: 546–37.

    Google Scholar 

  98. Kass IS, Lipton P. Mechanisms involved in irreversible anoxic damage to the in vitro rat hippocampal slice, J Physiol 1982; 332: 459–72.

    Google Scholar 

  99. Rothman SM. Synaptic release of excitatory amino neurotransmitter mediates anoxic neuronal death, J Neurosci 1984; 4: 1884–91.

    Google Scholar 

  100. Walz W, Hertz L. Functional interactions between neurons and astrocytes, II: Potassium homeostasis at the cellular level, Prog Neorobiol 1983; 20: 133–83.

    Google Scholar 

  101. Astrup, Symon L, Branston NM, Lassen NM. Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischaemia, Stroke 1977; 8: 51–7.

    Google Scholar 

  102. Neal MJ, Cunningham JR, Shah MA. Neuronal and glial release of GABA from the rat retina. In: Weiler R, Osborne NN, eds. Neurobiology of the inner retina. Berlin: Springer Verlag, 1989; 77–89.

    Google Scholar 

  103. Lam DMK. Development of neurotransmitter systems in the retina: biochemical, anatomical and physiological correlates. In: Tso MOM, ed. Retinal diseases; biomedical foundations and clinical management. Philadelphia: JB Lippincott Co, 1988: 103–11.

    Google Scholar 

  104. Bauer B, Ehinger B. Light-induced release of amino acids from the retina. In: Fonnum F, ed. Amino acids as chemical transmitters. New York: Plenum Press, 1978: 275–95.

    Google Scholar 

  105. Phillis JW, Walter GA. Effect of a brief hypoxic/hypotensive episode on the in vivo release of cerebral cortical gamma-aminobutyric acid and glycine, Brain Res 1989; 504: 121–3.

    Google Scholar 

  106. Rothman SM and Olney JW. Glutamate and the pathophysiology of hypoxic-ischaemic brain damage, Ann Neurol 1986; 19: 105–11.

    Google Scholar 

  107. Silvertein FS, Buchanan K, Johnston MV. Pertinatal hypoxia-ischaemia disrupts striatal high-affinity [3H]glutamate uptake into synaptosomes, J Neurochem 1986; 47: 1614–19.

    Google Scholar 

  108. Rothman SM, Olney JW. Excitotoxicity and the NMDA receptor, Trends Neurosci 1987; 10: 299–302.

    Google Scholar 

  109. Lucas DR, Newhouse JP. The toxic effect of sodium L-glutamate on the inner layers of the retina, AMA Arch Ophthalmol 1957; 58: 193–201.

    Google Scholar 

  110. Zivin JA, Choi DW. Stroke therapy, Sci Amer 1991; 265: 36–43.

    Google Scholar 

  111. Greenberger LM, Besharse JC. Stimulation of photoreceptor disc shedding and pigment epithelial phagocytosis by glutamate, aspartate and other amino acids, J Comp Neurol 1985; 239: 361–72.

    Google Scholar 

  112. Besharse JC, Spratt G. Excitatory amino acids and rod photoreceptor disc shedding: Analysis using specific agonists, Exp Eye Res 1988; 47: 609–20.

    Google Scholar 

  113. Choi DW. Ionic dependence of glutamate neurotoxicity, J. Neurosci 1987; 7: 369–379.

    Google Scholar 

  114. Olney JW. Neurotoxicity of excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL, eds. Kainic acid as a tool in neurobiology. New York: Raven, 1978: 95–121.

    Google Scholar 

  115. Daw NW, Fox K. Function of NMDA receptors in the developing visual cortex. In: Lam D M-K, Shatz CJ, eds. Development of the visual system. Proceedings of the Retina Research Foundation Symposia, Vol 3. Cambridge: MIT, 1991: 243–52.

    Google Scholar 

  116. Olney JW, Price MT, Samson L, Labruyere J. The role of specific ions in glutamate neurotoxicity, Neurosci 1982; 339–45.

  117. Choi DW. Cerebral hypoxia: Some new approaches and unanswered questions, J Neurosci 1990; 10: 2493–501.

    Google Scholar 

  118. Siesjo BK, Bengtsson F. Calcium fluxes, calcium antagonists and calcium-related pathology in brain ischaemia, hypoglycemia and spreading depression: A unifying hypothesis, J Cereb Blood Flow Metab 1989; 9: 127–40.

    Google Scholar 

  119. Mody I, Salter MW, MacDonald JF. Requirement of NMDA receptor-channels for intracellular high-energy phosphates and the extent of intraneuronal calcium buffering in cultured mouse hippocampal neurons, Neurosci Lett 1988; 93: 73–8.

    Google Scholar 

  120. Morad M, Dichter M, Tang CM. The NMDA activated current in hippocampal neurons is highly sensitive to [H+]0, Soc Neurosci Abstr 1988; 14: 791.

    Google Scholar 

  121. Giffard RG, Monyer H, Christine CW, Choi DW. Acidosis oxygen-glucose deprivation neuronal injury in cortical cultures, Brain Res 1990; 506: 339–42.

    Google Scholar 

  122. Tombaugh GC, Sapolsky RM. Mild acidosis protects hippocampal neurons from injury induced by oxygen and glucose deprivation, Brain Res 1990; 506: 343–5.

    Google Scholar 

  123. Simon RP, Griffiths T, Evans C, Swan JH, Meldrum BS. Calcium overload in selectively vulnerable neurons of the hippocampus during and after ischaemia: an electron microscopy study in the rat, J Cereb Blood Flow Metab 1984; 4: 350–61.

    Google Scholar 

  124. Baudry M, Bundman MC, Smith EK, Lynch GS. Micromolar calcium stimulates proteoysis and glutamate binding in rat brain synaptic membranes. Science 1981; 212: 937–8.

    Google Scholar 

  125. Choi DW, Peters S, Yokoyama M. Glutamate neurotoxicity in cortical cell culture is attenuated by N-methyl-D-aspartate receptor antagonists. Soc Neurosci Abst 1986; 12: 381.

    Google Scholar 

  126. Wolfe LS. Eicosanoids: prostaglandins, thromboxanes, leukotrienes and other derivatives of carbon-20 unsaturated fatty acids, J Neurochem 1982; 38: 1–14.

    Google Scholar 

  127. Barbour B, Szatkowski M, Ingledew N, Attwell D. Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells, Nature 1989; 342: 918–20.

    Google Scholar 

  128. Chan PH, Fishman RA, Longar S, Chen S, Yu A. Cellular and molecular effects of polyunsaturated fatty acids in brain ischaemia and injury, Prog Brain Res 1985; 63: 227–35.

    Google Scholar 

  129. Siesjo BK. Free radicals and brain damage, Cerebrovasc Brain Metab Rev 1989; 1: 165–211.

    Google Scholar 

  130. Farber JL, Chien KR, Mittnacht JR. The Pathogenesis of irreversible cell injury in ischaemia, Am J Pathol 1981; 102: 271–81.

    Google Scholar 

  131. Gilbert DS, Newby BJ, Anderton BH. Neurofilament disguise, destruction and discipline, Nature 1975; 256: 586–9.

    Google Scholar 

  132. Garthwaite G, Hajos F, Garthwaite J. Ionic requirements for neurotoxic effects of excitatory amino acid analogues in rat cerebellar slices, Neurosci 1986; 18: 437–47.

    Google Scholar 

  133. MacDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker JL. Optical measurement of calcium transients triggered by excitatory amino acids in spinal cord neurons under voltage clamp, Biophys J. 1986; 49: 365.

    Google Scholar 

  134. Nowak L, Bregestovski P, Ascher P. Magnesium gates glutamate activated channels in mouse central neurons, Nature 1984; 307: 462–5.

    Google Scholar 

  135. Weiss JH, Hartley DM, Koh J, Choi DW. The calcium channel blocker nifedipine attentuates slow excitatory amino acid neurotoxicity, Science 1990; 247: 1474–7.

    Google Scholar 

  136. Simon RP, Swan SH, Griffiths T, Meldrum BS. Blockade of N-methyl-D-aspartate receptors may protect against ischaemic damage in the brain, Science 1984; 226: 850–2.

    Google Scholar 

  137. Meldrum B, Garthwaite J. Excitatory amino acid neurotoxicity and neurodegenerative disease, Trends Pharmacol Sci 1990; 11: 379–87.

    Google Scholar 

  138. Yoon HY, Marmor MF. Dextromethorphan protects retina against ischemic injury in vivo, Arch Ophthalmol 1989; 107: 409–11.

    Google Scholar 

  139. Sternau LL, Lust Wd, Ricci AJ, Ratcheson R. Role of γ-aminobutyric acid in selective vulnerability in gerbils, Stroke 1989; 20: 281–7.

    Google Scholar 

  140. Reedy DP, Little JR, Capraro JA. Effects of verapamil on acute focal cerebral ischaemia, Neurosurgery 1983; 12: 272–6.

    Google Scholar 

  141. Hossman K-A, Paschen W, Csiba L. Relationship between calciun accumulation and recovery of cat brain after prolonged cerebral ischaemia, J Cereb Blood Flow Metab 1983; 3: 346–53.

    Google Scholar 

  142. Rhoads DE, Kaplan MA, Peterson NA, Raghupathy E. Effects of free fatty acids on synaptosomal amino acid uptake systems, J Neurochem 1982; 38: 1255–60.

    Google Scholar 

  143. Meldrum BS, Chapman AG, Patel S, Swan J. Competitive NMDA antagonists as drugs. In: Watkins JC, Collingridge GL, eds. The NMDA receptor. Oxford: Oxford University Press, 1989: 207–16.

    Google Scholar 

  144. Iversen LL, Woodruff GN, Kemp JA, Foster AC, McKernan R, Gill R, Wong EHF. Non-competitive NMDA antagonists as drugs. In: Watkins JC, Collingridge GL, eds. The NMDA receptor. Oxford: Oxford University Press, 1989: 217–26.

    Google Scholar 

  145. Choi DW, Koh J-Y, Peters S. Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists, J Neurosci 1988; 8: 185–96.

    Google Scholar 

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  1. Department of Optometry, University of Melbourne, Parkville, Australia

    Leonie N. Robin &  Michael Kalloniatis

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  1. Leonie N. Robin
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  2. Michael Kalloniatis
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Robin, L.N., Kalloniatis, M. Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA. Doc Ophthalmol 80, 273–300 (1992). https://doi.org/10.1007/BF00154376

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