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Immunology and Glaucoma

  • Michal Schwartz
  • Anat London
Chapter

Abstract

Glaucoma, although once thought of as a single disease, is actually a group of diseases of the optic nerve involving loss of retinal ganglion cells. The process of cell death occurs in a characteristic pattern of optic neuropathy - a broad term for a certain pattern of damage to the optic nerve (the bundle of nerve fibers that carries information from the eye to the brain). Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss that can progress to permanent blindness.

Keywords

Amyotrophic Lateral Sclerosis Optic Nerve Retinal Ganglion Cell Glatiramer Acetate Visual Field Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363:1711–1720.CrossRefPubMedGoogle Scholar
  2. 2.
    Burgoyne CF, Downs JC, Bellezza AJ, et al. The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res. 2005;24:39–73.CrossRefPubMedGoogle Scholar
  3. 3.
    Sigal IA, Flanagan JG, Ethier CR. Factors influencing optic nerve head biomechanics. Invest Ophthalmol Vis Sci. 2005;46:4189–4199.CrossRefPubMedGoogle Scholar
  4. 4.
    Tezel G, Wax MB. Hypoxia-inducible factor 1alpha in the glaucomatous retina and optic nerve head. Arch Ophthalmol. 2004;122:1348–1356.CrossRefPubMedGoogle Scholar
  5. 5.
    Tezel G, Hernandez R, Wax MB. Immunostaining of heat shock proteins in the retina and optic nerve head of normal and glaucomatous eyes. Arch Ophthalmol. 2000;118:511–518.PubMedGoogle Scholar
  6. 6.
    Quigley HA, Maumenee AE. Long-term follow-up of treated open-angle glaucoma. Am J Ophthalmol. 1979;87:519–525.PubMedGoogle Scholar
  7. 7.
    Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701-713. discussion 829–730.PubMedGoogle Scholar
  8. 8.
    Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003;121:48–56.PubMedGoogle Scholar
  9. 9.
    Johnson EC, Cepurna WO, Jia L, et al. The use of cyclodialysis to limit exposure to elevated intraocular pressure in rat glaucoma models. Exp Eye Res. 2006;83:51–60.CrossRefPubMedGoogle Scholar
  10. 10.
    Nickells RW, Schlamp CL, Li Y, et al. Surgical lowering of elevated intraocular pressure in monkeys prevents progression of glaucomatous disease. Exp Eye Res. 2007;84:729–736.CrossRefPubMedGoogle Scholar
  11. 11.
    Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:1268–1279.PubMedGoogle Scholar
  12. 12.
    Jay JL, Allan D. The benefit of early trabeculectomy versus conventional management in primary open angle glaucoma relative to severity of disease. Eye. 1989;3(Pt 5):528–535.PubMedGoogle Scholar
  13. 13.
    Nouri-Mahdavi K, Brigatti L, Weitzman M, et al. Outcomes of trabeculectomy for primary open-angle glaucoma. Ophthalmology. 1995;102:1760–1769.PubMedGoogle Scholar
  14. 14.
    Brubaker RF. Delayed functional loss in glaucoma. LII Edward Jackson Memorial Lecture. Am J Ophthalmol. 1996;121:473–483.PubMedGoogle Scholar
  15. 15.
    Richler M, Werner EB, Thomas D. Risk factors for progression of visual field defects in medically treated patients with glaucoma. Can J Ophthalmol. 1982;17:245–248.PubMedGoogle Scholar
  16. 16.
    Schulzer M, Drance SM, Carter CJ, et al. Biostatistical evidence for two distinct chronic open angle glaucoma populations. Br J Ophthalmol. 1990;74:196–200.CrossRefPubMedGoogle Scholar
  17. 17.
    Chauhan BC, Drance SM. The relationship between intraocular pressure and visual field progression in glaucoma. Graefes Arch Clin Exp Ophthalmol. 1992;230:521–526.CrossRefPubMedGoogle Scholar
  18. 18.
    Schwartz M, Belkin M, Yoles E, et al. Potential treatment modalities for glaucomatous neuropathy: neuroprotection and neuroregeneration. J Glaucoma. 1996;5:427–432.PubMedGoogle Scholar
  19. 19.
    Schwartz M. Neurodegeneration and neuroprotection in glaucoma: development of a therapeutic neuroprotective vaccine: the friedenwald lecture. Invest Ophthalmol Vis Sci. 2003;44:1407–1411.CrossRefPubMedGoogle Scholar
  20. 20.
    Schwartz M. Lessons for glaucoma from other neurodegenerative diseases: can one treatment suit them all? J Glaucoma. 2005;14:321–323.CrossRefPubMedGoogle Scholar
  21. 21.
    Beckman JS, Carson M, Smith CD, et al. ALS, SOD and peroxynitrite. Nature. 1993;364:584.CrossRefPubMedGoogle Scholar
  22. 22.
    Abe K, Pan LH, Watanabe M, et al. Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis. Neurosci Lett. 1995;199:152–154.CrossRefPubMedGoogle Scholar
  23. 23.
    Giasson BI, Duda JE, Murray IV, et al. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science. 2000;290:985–989.CrossRefPubMedGoogle Scholar
  24. 24.
    Castegna A, Thongboonkerd V, Klein JB, et al. Proteomic identification of nitrated proteins in Alzheimer’s disease brain. J Neurochem. 2003;85:1394–1401.CrossRefPubMedGoogle Scholar
  25. 25.
    Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat Med. 2004;10(Suppl):S18-S25.CrossRefPubMedGoogle Scholar
  26. 26.
    Potashkin JA, Meredith GE. The role of oxidative stress in the dysregulation of gene expression and protein metabolism in neurodegenerative disease. Antioxid Redox Signal. 2006;8:144–151.CrossRefPubMedGoogle Scholar
  27. 27.
    Sultana R, Poon HF, Cai J, et al. Identification of nitrated proteins in Alzheimer’s disease brain using a redox proteomics approach. Neurobiol Dis. 2006;22:76–87.CrossRefPubMedGoogle Scholar
  28. 28.
    Oku H, Yamaguchi H, Sugiyama T, et al. Retinal toxicity of nitric oxide released by administration of a nitric oxide donor in the albino rabbit. Invest Ophthalmol Vis Sci. 1997;38:2540–2544.PubMedGoogle Scholar
  29. 29.
    Levkovitch-Verbin H, Harris-Cerruti C, Groner Y, et al. RGC death in mice after optic nerve crush injury: oxidative stress and neuroprotection. Invest Ophthalmol Vis Sci. 2000;41:4169–4174.PubMedGoogle Scholar
  30. 30.
    Tezel G. Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res. 2006;25:490–513.CrossRefPubMedGoogle Scholar
  31. 31.
    Tezel G, Wax MB. Glial modulation of retinal ganglion cell death in glaucoma. J Glaucoma. 2003;12:63–68.CrossRefPubMedGoogle Scholar
  32. 32.
    Tezel G, Yang X, Cai J. Proteomic identification of oxidatively modified retinal proteins in a chronic pressure-induced rat model of glaucoma. Invest Ophthalmol Vis Sci. 2005;46:3177–3187.CrossRefPubMedGoogle Scholar
  33. 33.
    Martindale JL, Holbrook NJ. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol. 2002;192:1–15.CrossRefPubMedGoogle Scholar
  34. 34.
    Ritch R. Potential role for Ginkgo biloba extract in the treatment of glaucoma. Med Hypotheses. 2000;54:221–235.CrossRefPubMedGoogle Scholar
  35. 35.
    Siu AW, Maldonado M, Sanchez-Hidalgo M, et al. Protective effects of melatonin in experimental free radical-related ocular diseases. J Pineal Res. 2006;40:101–109.CrossRefPubMedGoogle Scholar
  36. 36.
    Neufeld AH, Sawada A, Becker B. Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc Natl Acad Sci U S A. 1999;96:9944–9948.CrossRefPubMedGoogle Scholar
  37. 37.
    Sahai S. Glutamate in the mammalian CNS. Eur Arch Psychiatry Clin Neurosci. 1990;240:121–133.CrossRefPubMedGoogle Scholar
  38. 38.
    Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994;330:613–622.CrossRefPubMedGoogle Scholar
  39. 39.
    Tsacopoulos M, Poitry-Yamate CL, MacLeish PR, et al. Trafficking of molecules and metabolic signals in the retina. Prog Retin Eye Res. 1998;17:429–442.CrossRefPubMedGoogle Scholar
  40. 40.
    Sucher NJ, Lipton SA, Dreyer EB. Molecular basis of glutamate toxicity in retinal ganglion cells. Vision Res. 1997;37:3483–3493.CrossRefPubMedGoogle Scholar
  41. 41.
    Siliprandi R, Canella R, Carmignoto G, et al. N-methyl-d-aspartate-induced neurotoxicity in the adult rat retina. Vis Neurosci. 1992;8:567–573.CrossRefPubMedGoogle Scholar
  42. 42.
    Dreyer EB. A proposed role for excitotoxicity in glaucoma. J Glaucoma. 1998;7:62–67.CrossRefPubMedGoogle Scholar
  43. 43.
    Napper GA, Pianta MJ, Kalloniatis M. Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions. Vis Neurosci. 1999;16:149–158.PubMedGoogle Scholar
  44. 44.
    Olney JW. Glutaate-induced retinal degeneration in neonatal mice. Electron microscopy of the acutely evolving lesion. J Neuropathol Exp Neurol. 1969;28:455–474.CrossRefPubMedGoogle Scholar
  45. 45.
    Olney JW, Price MT, Samson L, et al. The role of specific ions in glutamate neurotoxicity. Neurosci Lett. 1986;65:65–71.CrossRefPubMedGoogle Scholar
  46. 46.
    Van Den Bosch L, Van Damme P, Bogaert E, et al. The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim Biophys Acta. 2006;1762:1068–1082.Google Scholar
  47. 47.
    Riederer P, Hoyer S. From benefit to damage. Glutamate and advanced glycation end products in Alzheimer brain. J Neural Transm. 2006;113:1671–1677.CrossRefPubMedGoogle Scholar
  48. 48.
    Lipton SA. Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation. Curr Drug Targets. 2007;8:621–632.CrossRefPubMedGoogle Scholar
  49. 49.
    Beal MF. Excitotoxicity and nitric oxide in Parkinson’s disease pathogenesis. Ann Neurol. 1998;44:S110–114.CrossRefPubMedGoogle Scholar
  50. 50.
    Lancelot E, Beal MF. Glutamate toxicity in chronic neurodegenerative disease. Prog Brain Res. 1998;116:331–347.CrossRefPubMedGoogle Scholar
  51. 51.
    Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988;1:623–634.CrossRefPubMedGoogle Scholar
  52. 52.
    Stuiver BT, Douma BR, Bakker R, et al. In vivo protection against NMDA-induced neurodegeneration by MK-801 and nimodipine: combined therapy and temporal course of protection. Neurodegeneration. 1996;5:153–159.CrossRefPubMedGoogle Scholar
  53. 53.
    Choi DW. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 1988;11:465–469.CrossRefPubMedGoogle Scholar
  54. 54.
    Takahashi K, Lam TT, Edward DP, et al. Protective effects of flunarizine on ischemic injury in the rat retina. Arch Ophthalmol. 1992;110:862–870.PubMedGoogle Scholar
  55. 55.
    Bath CP, Farrell LN, Gilmore J, et al. The effects of ifenprodil and eliprodil on voltage-dependent Ca2+ channels and in gerbil global cerebral ischaemia. Eur J Pharmacol. 1996;299:103–112.CrossRefPubMedGoogle Scholar
  56. 56.
    Mansour-Robaey S, Clarke DB, Wang YC, et al. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci U S A. 1994;91:1632–1636.CrossRefPubMedGoogle Scholar
  57. 57.
    Peinado-Ramon P, Salvador M, Villegas-Perez MP, et al. Effects of axotomy and intraocular administration of NT-4, NT-3, and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells. A quantitative in vivo study. Invest Ophthalmol Vis Sci. 1996;37:489–500.PubMedGoogle Scholar
  58. 58.
    Gao H, Qiao X, Hefti F, et al. Elevated mRNA expression of brain-derived neurotrophic factor in retinal ganglion cell layer after optic nerve injury. Invest Ophthalmol Vis Sci. 1997;38:1840–1847.PubMedGoogle Scholar
  59. 59.
    Klocker N, Cellerino A, Bahr M. Free radical scavenging and inhibition of nitric oxide synthase potentiates the neurotrophic effects of brain-derived neurotrophic factor on axotomized retinal ganglion cells in vivo. J Neurosci. 1998;18:1038–1046.PubMedGoogle Scholar
  60. 60.
    Rocha M, Martins RA, Linden R. Activation of NMDA receptors protects against glutamate neurotoxicity in the retina: evidence for the involvement of neurotrophins. Brain Res. 1999;827:79–92.CrossRefPubMedGoogle Scholar
  61. 61.
    Unoki K, LaVail MM. Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor. Invest Ophthalmol Vis Sci. 1994;35:907–915.PubMedGoogle Scholar
  62. 62.
    Lansbury PT, Lashuel HA. A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature. 2006;443:774–779.CrossRefPubMedGoogle Scholar
  63. 63.
    McKinnon SJ, Lehman DM, Kerrigan-Baumrind LA, et al. Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension. Invest Ophthalmol Vis Sci. 2002;43:1077–1087.PubMedGoogle Scholar
  64. 64.
    Weydt P, La Spada AR. Targeting protein aggregation in neurodegeneration - lessons from polyglutamine disorders. Expert Opin Ther Targets. 2006;10:505–513.CrossRefPubMedGoogle Scholar
  65. 65.
    Oltvai ZN, Korsmeyer SJ. Checkpoints of dueling dimers foil death wishes. Cell. 1994;79:189–192.CrossRefPubMedGoogle Scholar
  66. 66.
    Levin LA, Schlamp CL, Spieldoch RL, et al. Identification of the bcl-2 family of genes in the rat retina. Invest Ophthalmol Vis Sci. 1997;38:2545–2553.PubMedGoogle Scholar
  67. 67.
    Thornberry NA. Caspases: key mediators of apoptosis. Chem Biol. 1998;5:R97–103.CrossRefPubMedGoogle Scholar
  68. 68.
    Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998;281:1312–1316.CrossRefPubMedGoogle Scholar
  69. 69.
    Quigley HA. Neuronal death in glaucoma. Prog Retin Eye Res. 1999;18:39–57.CrossRefPubMedGoogle Scholar
  70. 70.
    Gupta N, Yucel YH. Glaucoma as a neurodegenerative disease. Curr Opin Ophthalmol. 2007;18:110–114.CrossRefPubMedGoogle Scholar
  71. 71.
    Mozaffarieh M, Flammer J. Is there more to glaucoma treatment than lowering IOP? Surv Ophthalmol. 2007;52(Suppl 2):S174–179.CrossRefPubMedGoogle Scholar
  72. 72.
    Nickells RW. From ocular hypertension to ganglion cell death: a heoretical sequence of events leading to glaucoma. Can J Ophthalmol. 2007;42:278–287.CrossRefPubMedGoogle Scholar
  73. 73.
    Hartwick AT. Beyond intraocular pressure: neuroprotective strategies for future glaucoma therapy. Optom Vis Sci. 2001;78:85–94.CrossRefPubMedGoogle Scholar
  74. 74.
    Chidlow G, Wood JP, Casson RJ. Pharmacological neuroprotection for glaucoma. Drugs. 2007;67:725–759.CrossRefPubMedGoogle Scholar
  75. 75.
    Moalem G, Leibowitz-Amit R, Yoles E, et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med. 1999;5:49–55.CrossRefPubMedGoogle Scholar
  76. 76.
    Fisher J, Levkovitch-Verbin H, Schori H, et al. Vaccination for neuroprotection in the mouse optic nerve: implications for optic neuropathies. J Neurosci. 2001;21:136–142.PubMedGoogle Scholar
  77. 77.
    Mizrahi T, Hauben E, Schwartz M. The tissue-specific self-pathogen is the protective self-antigen: the case of uveitis. J Immunol. 2002;169:5971–5977.PubMedGoogle Scholar
  78. 78.
    Yoles E, Hauben E, Palgi O, et al. Protective autoimmunity is a physiological response to CNS trauma. J Neurosci. 2001;21:3740–3748.PubMedGoogle Scholar
  79. 79.
    Schori H, Kipnis J, Yoles E, et al. Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: implications for glaucoma. Proc Natl Acad Sci U S A. 2001;98:3398–3403.CrossRefPubMedGoogle Scholar
  80. 80.
    Avidan H, Kipnis J, Butovsky O, et al. Vaccination with autoantigen protects against aggregated beta-amyloid and glutamate toxicity by controlling microglia: effect of CD4+CD25+ T cells. Eur J Immunol. 2004;34:3434–3445.CrossRefPubMedGoogle Scholar
  81. 81.
    Bakalash S, Kipnis J, Yoles E, et al. Resistance of retinal ganglion cells to an increase in intraocular pressure is immune-dependent. Invest Ophthalmol Vis Sci. 2002;43:2648–2653.PubMedGoogle Scholar
  82. 82.
    Bakalash S, Kessler A, Mizrahi T, et al. Antigenic specificity of immunoprotective therapeutic vaccination for glaucoma. Invest Ophthalmol Vis Sci. 2003;44:3374–3381.CrossRefPubMedGoogle Scholar
  83. 83.
    Moalem G, Gdalyahu A, Shani Y, et al. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun. 2000;15:331–345.CrossRefPubMedGoogle Scholar
  84. 84.
    Butovsky O, Hauben E, Schwartz M. Morphological aspects of spinal cord autoimmune neuroprotection: colocalization of T cells with B7-2 (CD86) and prevention of cyst formation. FASEB J. 2001;15:1065–1067.PubMedGoogle Scholar
  85. 85.
    Barouch R, Schwartz M. Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: implications for protective autoimmunity. FASEB J. 2002;16:1304–1306.PubMedGoogle Scholar
  86. 86.
    Butovsky O, Talpalar AE, Ben-Yaakov K, et al. Activation of microglia by aggregated beta-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-gamma and IL-4 render them protective. Mol Cell Neurosci. 2005;29:381–393.CrossRefPubMedGoogle Scholar
  87. 87.
    Shaked I, Tchroesh D, Gersner R, et al. Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem. 2005;92:997–1009.CrossRefPubMedGoogle Scholar
  88. 88.
    Kipnis J, Mizrahi T, Hauben E, et al. Neuroprotective autoimmunity: naturally occurring CD4+CD25+ regulatory T cells suppress the ability to withstand injury to the central nervous system. Proc Natl Acad Sci USA. 2002;99:15620–15625.CrossRefPubMedGoogle Scholar
  89. 89.
    Kipnis J, Cardon M, Avidan H, et al. Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity: implications for neurodegeneration. J Neurosci. 2004;24:6133–6143.CrossRefPubMedGoogle Scholar
  90. 90.
    Kipnis J, Yoles E, Porat Z, et al. T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc Natl Acad Sci U S A. 2000;97:7446–7451.CrossRefPubMedGoogle Scholar
  91. 91.
    Benner EJ, Mosley RL, Destache CJ, et al. Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101:9435–9440.CrossRefPubMedGoogle Scholar
  92. 92.
    Schwartz M. Modulating the immune system: a vaccine for glaucoma? Can J Ophthalmol. 2007;42:439–441.CrossRefPubMedGoogle Scholar
  93. 93.
    Hauben E, Agranov E, Gothilf A, et al. Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease. J Clin Invest. 2001;108:591–599.PubMedGoogle Scholar
  94. 94.
    Bakalash S, Shlomo GB, Aloni E, et al. T-cell-based vaccination for morphological and functional neuroprotection in a rat model of chronically elevated intraocular pressure. J Mol Med. 2005;83:904–916.CrossRefPubMedGoogle Scholar
  95. 95.
    Blair M, Pease ME, Hammond J, et al. Effect of glatiramer acetate on primary and secondary degeneration of retinal ganglion cells in the rat. Invest Ophthalmol Vis Sci. 2005;46:884–890.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michal Schwartz
    • 1
  • Anat London
    • 1
  1. 1.Department of NeurobiologyThe Weizmann Institute of ScienceRehovotIsrael

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