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Published in: Japanese Journal of Ophthalmology 5/2016

01-09-2016 | Laboratory Investigation

Rescue effects of intravenous immunoglobulin on optic nerve degeneration in a rat model of neuromyelitis optica

Authors: Sho Nobuyoshi, Akiyasu Kanamori, Yoshiko Matsumoto, Makoto Nakamura

Published in: Japanese Journal of Ophthalmology | Issue 5/2016

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Abstract

Purpose

Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that predominantly attacks the optic nerve and spinal cord. This study evaluated the effect of administration of human IgG (hIgG) into the caudal vein on optic nerve degeneration in a rodent model of NMO.

Methods

The optic nerves were exposed to AQP4-Ab-positive sera, and the administration of intravenous immunoglobulin (IVIG) was performed immediately, at 7 days (cohort A) or at 7 days and 10 days (cohort B) after exposure to the sera. A reference group, similarly exposed to the serum, was treated with saline. Retinal ganglion cells (RGCs) labeled by the injection of Fluoro-Gold into the superior colliculus were counted in whole-mounted retina. RGCs labeled by the injection of Fluoro-Gold into the superior colliculus were counted in the whole-mounted retina.

Results

The number of RGCs 14 days after optic nerve exposure to sera from patients with NMO was 1455 ± 192/mm2 (n = 7) in cohort A, 1657 ± 192/mm2 (n = 4) in cohort B, and 981 ± 182/mm2 (n = 10) in the saline-treated reference group (p < 0.001). Western blotting revealed that the content of neurofilament in the optic nerve of the hIgG-treated group in cohort A was significantly greater than that in the reference group (p = 0.037).

Conclusions

IVIG administration reduced optic nerve degeneration in a rat model of NMO-optic neuritis. IVIG could be used as a treatment in the acute phase of NMO.
Literature
1.
go back to reference Wingerchuk DM. Neuromyelitis optica: potential roles for intravenous immunoglobulin. J Clin Immunol. 2013;33(Suppl 1):S33–7.CrossRefPubMed Wingerchuk DM. Neuromyelitis optica: potential roles for intravenous immunoglobulin. J Clin Immunol. 2013;33(Suppl 1):S33–7.CrossRefPubMed
2.
go back to reference Wiles CM, Brown P, Chapel H, Guerrini R, Hughes RA, Martin TD, et al. Intravenous immunoglobulin in neurological disease: a specialist review. J Neurol Neurosurg Psychiatry. 2002;72:440–8.PubMedPubMedCentral Wiles CM, Brown P, Chapel H, Guerrini R, Hughes RA, Martin TD, et al. Intravenous immunoglobulin in neurological disease: a specialist review. J Neurol Neurosurg Psychiatry. 2002;72:440–8.PubMedPubMedCentral
3.
go back to reference Berger M, McCallus DE, Lin CS. Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies. J Peripher Nerv Syst. 2013;18:275–96.CrossRefPubMedPubMedCentral Berger M, McCallus DE, Lin CS. Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies. J Peripher Nerv Syst. 2013;18:275–96.CrossRefPubMedPubMedCentral
4.
go back to reference Jacob S, Rajabally YA. Current proposed mechanisms of action of intravenous immunoglobulins in inflammatory neuropathies. Curr Neuropharmacol. 2009;7:337–42.CrossRefPubMedPubMedCentral Jacob S, Rajabally YA. Current proposed mechanisms of action of intravenous immunoglobulins in inflammatory neuropathies. Curr Neuropharmacol. 2009;7:337–42.CrossRefPubMedPubMedCentral
5.
go back to reference Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012;367:2015–25.CrossRefPubMed Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012;367:2015–25.CrossRefPubMed
6.
go back to reference Bakker J, Metz L. Devic’s neuromyelitis optica treated with intravenous gamma globulin (IVIG). Can J Neurol Sci. 2004;31:265–7.CrossRefPubMed Bakker J, Metz L. Devic’s neuromyelitis optica treated with intravenous gamma globulin (IVIG). Can J Neurol Sci. 2004;31:265–7.CrossRefPubMed
7.
go back to reference Okada K, Tsuji S, Tanaka K. Intermittent intravenous immunoglobulin successfully prevents relapses of neuromyelitis optica. Intern Med. 2007;46:1671–2.CrossRefPubMed Okada K, Tsuji S, Tanaka K. Intermittent intravenous immunoglobulin successfully prevents relapses of neuromyelitis optica. Intern Med. 2007;46:1671–2.CrossRefPubMed
8.
go back to reference Magraner MJ, Coret F, Casanova B. The effect of intravenous immunoglobulin on neuromyelitis optica. Neurologia. 2013;28:65–72.CrossRefPubMed Magraner MJ, Coret F, Casanova B. The effect of intravenous immunoglobulin on neuromyelitis optica. Neurologia. 2013;28:65–72.CrossRefPubMed
9.
go back to reference Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler. 2014;20:501–4.CrossRefPubMed Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler. 2014;20:501–4.CrossRefPubMed
10.
go back to reference Matsumoto Y, Kanamori A, Nakamura M, Takahashi T, Nakashima I, Negi A. Sera from patients with seropositive neuromyelitis optica spectral disorders caused the degeneration of rodent optic nerve. Exp Eye Res. 2014;119:61–9.CrossRefPubMed Matsumoto Y, Kanamori A, Nakamura M, Takahashi T, Nakashima I, Negi A. Sera from patients with seropositive neuromyelitis optica spectral disorders caused the degeneration of rodent optic nerve. Exp Eye Res. 2014;119:61–9.CrossRefPubMed
11.
go back to reference Kanamori A, Catrinescu MM, Kanamori N, Mears KA, Beaubien R, Levin LA. Superoxide is an associated signal for apoptosis in axonal injury. Brain. 2010;133:2612–25.CrossRefPubMedPubMedCentral Kanamori A, Catrinescu MM, Kanamori N, Mears KA, Beaubien R, Levin LA. Superoxide is an associated signal for apoptosis in axonal injury. Brain. 2010;133:2612–25.CrossRefPubMedPubMedCentral
12.
go back to reference Kanamori A, Naka M, Fukuda M, Nakamura M, Negi A. Latanoprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo. Exp Eye Res. 2009;88:535–41.CrossRefPubMed Kanamori A, Naka M, Fukuda M, Nakamura M, Negi A. Latanoprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo. Exp Eye Res. 2009;88:535–41.CrossRefPubMed
13.
go back to reference Ratelade J, Smith AJ, Verkman AS. Human immunoglobulin G reduces the pathogenicity of aquaporin-4 autoantibodies in neuromyelitis optica. Exp Neurol. 2014;255:145–53.CrossRefPubMedPubMedCentral Ratelade J, Smith AJ, Verkman AS. Human immunoglobulin G reduces the pathogenicity of aquaporin-4 autoantibodies in neuromyelitis optica. Exp Neurol. 2014;255:145–53.CrossRefPubMedPubMedCentral
14.
go back to reference Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133:349–61.CrossRefPubMedPubMedCentral Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133:349–61.CrossRefPubMedPubMedCentral
15.
go back to reference Asavapanumas N, Ratelade J, Verkman AS. Unique neuromyelitis optica pathology produced in naive rats by intracerebral administration of NMO-IgG. Acta Neuropathol. 2014;127:539–51.CrossRefPubMed Asavapanumas N, Ratelade J, Verkman AS. Unique neuromyelitis optica pathology produced in naive rats by intracerebral administration of NMO-IgG. Acta Neuropathol. 2014;127:539–51.CrossRefPubMed
16.
go back to reference Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013;12:554–62.CrossRefPubMed Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013;12:554–62.CrossRefPubMed
17.
go back to reference Berger M, Rosenkranz P, Brown CY. Intravenous and standard immune serum globulin preparations interfere with uptake of 125I-C3 onto sensitized erythrocytes and inhibit hemolytic complement activity. Clin Immunol Immunopathol. 1985;34:227–36.CrossRefPubMed Berger M, Rosenkranz P, Brown CY. Intravenous and standard immune serum globulin preparations interfere with uptake of 125I-C3 onto sensitized erythrocytes and inhibit hemolytic complement activity. Clin Immunol Immunopathol. 1985;34:227–36.CrossRefPubMed
Metadata
Title
Rescue effects of intravenous immunoglobulin on optic nerve degeneration in a rat model of neuromyelitis optica
Authors
Sho Nobuyoshi
Akiyasu Kanamori
Yoshiko Matsumoto
Makoto Nakamura
Publication date
01-09-2016
Publisher
Springer Japan
Published in
Japanese Journal of Ophthalmology / Issue 5/2016
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-016-0454-0

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