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Ischämie und Hypoxie

Ein Erklärungsversuch zur unterschiedlichen Absterberate retinaler Ganglienzellen bei Glaukom

Ischemia and hypoxia

An attempt to explain the different rates of retinal ganglion cell death in glaucoma

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Zusammenfassung

Bei der Hypoxie bzw. Ischämie werden die Rezeptoren der Ganglienzellen durch Freisetzung von Neurotransmittern überstimuliert. Glutamat und GABA (γ-Aminobuttersäure) sind die entscheidenden Neurotransmitter in der Retina. Es wird vermutet, dass das Ausmaß des Zelltods vom Grad der Depolarisation abhängt, die wiederum von der Anzahl der exzitatorischen (Glutamat) bzw. inhibitorischen (GABA) Rezeptoren der entsprechenden Ganglienzelle bestimmt wird.

Es wird dabei von der Vermutung ausgegangen, dass das Rezeptorprofil der individuellen Ganglienzelle die Sensitivität dieser Zelle gegenüber der Hypoxie bzw. Ischämie, d. h. die Zeit bis zum Untergang, bestimmt und somit ursächlich für die unterschiedliche Absterberate dieser Zellen bei primär chronischem Offenwinkelglaukom (PCOWG) ist.

Die Erforschung dieses Rezeptorprofils könnte für den Ansatz einer neuroprotektiven Behandlung des PCOWG von entscheidender Bedeutung sein.

Abstract

In hypoxic or ischemic states, the receptors of the ganglion cells are overstimulated by release of neurotransmitters. Glutamate and GABA (γ-aminobutyric acid) are the decisive neurotransmitters in the retina. It is presumed that the extent of cell death depends on the degree of depolarization, which in turn is determined by the amount of excitatory (glutamate) or inhibitory (GABA) receptors of the corresponding ganglion cell.

The assumption is that the receptor profile of the individual ganglion cells determines the sensitivity of these cells to hypoxia or ischemia, i.e., the time up to cell death, and thus represents the underlying cause of the different rates of cell death in primary chronic open-angle glaucoma.

Research on this receptor profile could be of pivotal importance for the approach to neuroprotective treatment of primary chronic open-angle glaucoma.

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Literatur

  1. Anderson RS, O’Brien C (1997) Psychophysical evidence for a selective loss of M ganglion cells in glaucoma. Vision Res 37:1079–1083

    Article  CAS  PubMed  Google Scholar 

  2. Baldridge WH (1996) Optical recordings of the effects of cholinergic ligands on neurons in the ganglion cell layer of mammalian retina. J Neurosci 16:5060–5072

    Google Scholar 

  3. Better B, Mulle C (1995) Review: neurotransmitter receptors. IL AMPA and kainate receptors. Neuropharmacology 34:123–139

    Article  PubMed  Google Scholar 

  4. Brunken WJ, Jin XT, Pis-Lopez AM (1993) The properties of the serotonergic system in the retina. In: Osborne NN, Chader GJ (eds) Progress in Retinal Research. Pergamon, Oxford, S 75–100

  5. Caprioli J, Kitano S (1993) Large ganglion cells are more susceptible to excitotoxic and hypoxic injury than small cells. Invest Ophthalmol Vis Sci 34:1429–1434

    Google Scholar 

  6. Cazevielle C, Osborne NN (1997) Retinal neurones containing kainate receptors are influenced by exogenous kainate and ischaema is while neurones lacking these receptors are not — melatonin counteracts the effect of ischaema and kainate. Brain Res 755:91–100

    Article  PubMed  Google Scholar 

  7. Chen Q, Olney JW, Lukasiewicz PD, Almli T, Romano C (1998) Ca2+-independent excitotoxic neurodegeneration in isolated retina, an intact neural net: a role for Cl− and inhibitory transmitters. Mol Pharmacol 53:564–572

    CAS  PubMed  Google Scholar 

  8. Dreyer EB, Pan ZH, Storm S, Lipton SA (1994) Greater sensitivity of larger retinal ganglion cells to NMDA-mediated cell death. Neuroreport 5:629–631

    CAS  PubMed  Google Scholar 

  9. Dreyer EB, Zurakowski D, Schumer RA, Podos SM, Lipton SA (1996) Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Arch Ophthalmol 114:299–305

    Google Scholar 

  10. Fechtner RD, Weinreb RN (1994) Mechanisms of optic nerve damage in primary open angle glaucoma. Surv Ophthalmol 39:23–42

    CAS  PubMed  Google Scholar 

  11. Flammer J (1995) To what extent are vascular factors involved in the pathogenesis of glaucoma? In: Kaiser HJ, Flammer J, Hendrickson P (Hrsg) Ocular Blood Flow. Glaucoma meeting. Karger, Basel, S 12–39

  12. Galzi JL, Changeux JP (1995) Neuronal nicotinic receptors: molecular organization and regulations. Neuropharmacology 34:563–582

    Article  CAS  PubMed  Google Scholar 

  13. Hessemer V, Schmidt KG (1997) Influence of the vasodilator drug isosorbide dinitrate on ocular circulation. Arch Ophthalmol 115:324–327

    Google Scholar 

  14. Klingmüller V, Schmidt KG, v Rückmann A, Gumbrecht S, Stein A, Koch B (2000) Farb- und Spektral-Doppler-sonographische Perfusionsmessungen in den kurzen hinteren Ziliararterien bei gesunden Probanden. In: Schmidt KG, Pillunat LE (Hrsg) Fortbildung Glaukom, Bd 3. Enke, Stuttgart, S 29–38

  15. Lipton SA (1988) Spontaneous release of acetylcholine affects the physiological nicotinic responses of rat retinal ganglion cells in culture. J Neurosci 8:3857–3868

    Google Scholar 

  16. Lukasiewicz PD, Shields CR (1998) Different combinations of GABAA and GABAc receptors confer distinct temporal properties to retinal synaptic responses. J Neurophysiol 79:3157–3167

    Google Scholar 

  17. Lyden PD (1997) GABA and neuroprotection. Int Rev Neurobiol 40:47–70

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Müller A, Villain M, Bonne C (1997) The release of amino acids from ischemic retina (letter). Exp Eye Res 64:291–293

    Article  PubMed  Google Scholar 

  20. Nguyen Legros J, Simon A, Caille I, Bloch B (1997) Immunocytochemical localization of dopamine D1 receptors in the retina of mammals. Vis Neurosci 14:545–551

    Google Scholar 

  21. Obrenovitch TP, Richards DA (1995) Extracellular neurotransmitter changes in cerebral ischaemia. Cerebrovasc Brain Metab Rev 7:1–54

    CAS  PubMed  Google Scholar 

  22. Osborne NN, Ugarte M, Chao M, Chidlow G, Bae JH, Wood JPM, Nash MS (1999) Neuroprotection in relation to retinal ischemia and relevance to glaucoma. Surv Ophthalmol 43 [Suppl 1]:S102–S128

    Article  PubMed  Google Scholar 

  23. Osborne NN, Wood JP, Chidlow G, Bae JH, Melena J, Nash MS (1999) Ganglion cell death in glaucoma: what do we really know? Br J Ophthalmol 83:980–986

    CAS  PubMed  Google Scholar 

  24. Osborne NN, DeSantis L, Melena J, Chidlow G, Wood JPM (2000) Attenuation of ganglion cell dysfunction. Ophthal Clin North Am 13:123–130

    Google Scholar 

  25. Osborne NN, Chidlow G, Wood JPM, Schmidt KG, Casson R, Melena J (2001) Expectations in the treatment of retinal diseases: neuroprotection. Curr Eye Res 22:321–332

    Article  CAS  PubMed  Google Scholar 

  26. Otori Y, Wei JY, Barnstable CJ (1998) Neurotoxic effects of low doses of glutamate on purified rat retinal ganglion cells. Invest Ophthalmol Vis Sci 39:972–981

    CAS  PubMed  Google Scholar 

  27. Pillunat LE, Stodtmeister R, Willmanns I (1987) Pressure compliance of the optic nerve head in low tension glaucoma. Br J Ophthalmol 71:181–187

    CAS  PubMed  Google Scholar 

  28. Pillunat LE, Stodtmeister R, Marquardt R, Mattern A (1989) Ocular perfusion pressures in different types of glaucoma. Int Ophthalmol 13:37–42

    CAS  PubMed  Google Scholar 

  29. Quigley HA, Sanchez RM, Dunkelberger GR, Baginski TA (1987) Chronic glaucoma selectively damages large optic nerve fibers. Invest Ophthalmol Vis Sci 28:913–920

    CAS  PubMed  Google Scholar 

  30. Quigley HA, Nickells RW, Kerigan LA et al (1995) Retinal cell ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 36:774–786

    CAS  PubMed  Google Scholar 

  31. Schmidt KG, Stegman DY, Serle JB et al. (1991) Ocular pulse amplitude in primary open-angle glaucoma, low tension glaucoma, and in ocular hypertensive patients before and after topical drug treatment. Invest Ophthalmol Vis Sci 32 [Suppl]:943

    Google Scholar 

  32. Schmidt KG, Mittag TW, Pavlovic S, Hessemer V (1996) Influence of physical exercise and nifedipine on ocular pulse amplitude. Graefes Arch Clin Exp Ophthalmol 234:527–532

    Google Scholar 

  33. Schmidt KG, v. Rückmann A, Geyer O, Mittag TW (1997) Einfluß des Nifedipins auf die okuläre Pulsamplitude bei Normaldruckglaukom. Klin Monatsbl Augenheilkd 210:355–359

    CAS  PubMed  Google Scholar 

  34. Schmidt KG, v Rückmann A, Mittag TW, Hessemer V, Pillunat LE (1997) Reduced ocular pulse amplitude in low-tension glaucoma is independent of vasospasm. Eye 11:485–488

    PubMed  Google Scholar 

  35. Schmidt KG, v Rückmann A, Pillunat LE (1998) Dorzolamide increases ocular pulse amplitude in high tension primary open angle glaucoma. Br J Ophthalmol 82:758–762

    CAS  PubMed  Google Scholar 

  36. Schmidt KG (1999) Antiglaukomatosa und choroidale Perfusion bei primärem und experimentell induziertem Offenwinkelglaukom. In: Schmidt KG, Pillunat LE (Hrsg) Fortbildung Glaukom, Bd 1, Perfusion und Pharmakologie. Enke, Stuttgart, S 39–50

  37. Schmidt KG, Klingmüller V, v Rückmann A, Koch B (2000) Retrobulbäre und chorioidale Hämodynamik bei Hochdruck- und Normaldruckglaukom. In: Schmidt KG, Pillunat LE (Hrsg) Fortbildung Glaukom, Bd 3. Enke, Stuttgart, S 103–114

  38. Schmidt KG, Klingmüller V, Gouveia SM, Osborne NN, Pillunat LE (2003) Short posterior ciliary artery, central retinal artery, and choroidal hemodynamics in brimonidine-treated primary open-angle glaucoma patients. Am J Ophthalmol 136:1038–1048

    Article  CAS  PubMed  Google Scholar 

  39. Schmidt KG, Geyer O, Mittag TW (2004) Adenylyl and guanylyl cyclase activity in the choroid. Exp Eye Res 78:901–907

    Google Scholar 

  40. Shimohama S, Akaike A, Kimura J (1996) Nicotine-induced protection against glutamate cytotoxicity. Nicotinic cholinergic receptor-mediated inhibition of nitric oxide formation. Ann N Y Acad Sci 777:356–361

    CAS  PubMed  Google Scholar 

  41. Shuaib A, Murabit MA, Kanthan R, Howlett W, Wishart T (1996) The neuroprotective effects of gamma-vinyl GABA in transient global ischemia: a morphological study with early and delayed evaluations. Neurosci Lett 204:1–4

    Article  CAS  PubMed  Google Scholar 

  42. Steinsapir KD, Goldberg RA (1994) Traumatic optic neuropathy. Surv Ophthalmol 38:487–518

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Augenklinik, Universität, Dresden

    K.-G. Schmidt & L. E. Pillunat

  2. Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, U.K.

    N. N. Osborne

  3. Augenklinik, Universität, Fetscherstraße 74, 01307 , Dresden

    K.-G. Schmidt

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  1. K.-G. Schmidt
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  2. L. E. Pillunat
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  3. N. N. Osborne
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Correspondence to K.-G. Schmidt.

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Schmidt, KG., Pillunat, L.E. & Osborne, N.N. Ischämie und Hypoxie. Ophthalmologe 101, 1071–1075 (2004). https://doi.org/10.1007/s00347-004-1131-0

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