Contributions
Abstract: 107
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Pathology
Objective: Neuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the CNS characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of neurodegeneration via glia-neuron interaction or activation of microglia in NMO.
Methods: Using 27 tissue blocks from 13 cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the anterior visual pathway (AVP).
Results: Lesions of NMO were characterized by the followings, compared to multiple sclerosis:
1) longitudinally extensive optic neuritis;
2) unique AQP4 dynamics -
(i) loss of AQP4 immunoreactivity on astrocytes with complement activation in optic nerve (ON) lesions,
(ii) loss of AQP4 immunoreactivity on Müller cells with no deposition of complement in the retinas, and
(iii) densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary antero/retrograde degeneration in the ON and retinal nerve fiber layer (RNFL);
3) more severe neurodegeneration -
(i) axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology,
(ii) mild loss of horizontal cells, and
(iii) RNFL thinning and loss of ganglion cells with abundance of AQP4+ astrocytes, indicating secondary retrograde degeneration after optic neuritis; and
4) increased meningeal and parenchymal inflammation with CD45RO+ T cells and Iba-1+/MHC class II+ microglia/macrophages in ON lesions. The presence of neurodegeneration in AQP4-deficient regions including myelin-preserved periplaque white matter adjacent the optic nerve plaques and the retina, which is physiologically devoid of myelin, may indicate that demyelination is not necessarily essential for processes of neurodegeneration in NMO.
Conclusion: Severe and widespread neuroaxonal damage with unique dynamics of AQP4 expression on astrocytes/Müller cells and substantial amounts of activated microgila/macrophages were prominent in NMO lesions of the AVP and may be associated with poor recovery in visual function of NMO.
Disclosure:
I. Kawachi has received funding for travel/speaker honoraria or for serving on scientific advisory boards from Novartis, Biogen, Bayer, Mitsubishi Tanabe and Takeda, and research support from a JSPS KAKENHI Grant.
M. Nishizawa has received funding for travel/speaker honoraria from Bayer, Novartis, Otsuka, Genzyme and Kissei, and research support from a Neuroimmunological Disease Research Committee grant from the Ministry of Health, Labor and Welfare, Japan.
M. Hokari, A. Yokoseki, A. Musashi, E. Saji, K. Yanagawa, F. Yanagimura, Y. Toyoshima, A. Kakita, H. Takahashi, and O. Onodera have nothing to disclose.
Abstract: 107
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Pathology
Objective: Neuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the CNS characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of neurodegeneration via glia-neuron interaction or activation of microglia in NMO.
Methods: Using 27 tissue blocks from 13 cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the anterior visual pathway (AVP).
Results: Lesions of NMO were characterized by the followings, compared to multiple sclerosis:
1) longitudinally extensive optic neuritis;
2) unique AQP4 dynamics -
(i) loss of AQP4 immunoreactivity on astrocytes with complement activation in optic nerve (ON) lesions,
(ii) loss of AQP4 immunoreactivity on Müller cells with no deposition of complement in the retinas, and
(iii) densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary antero/retrograde degeneration in the ON and retinal nerve fiber layer (RNFL);
3) more severe neurodegeneration -
(i) axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology,
(ii) mild loss of horizontal cells, and
(iii) RNFL thinning and loss of ganglion cells with abundance of AQP4+ astrocytes, indicating secondary retrograde degeneration after optic neuritis; and
4) increased meningeal and parenchymal inflammation with CD45RO+ T cells and Iba-1+/MHC class II+ microglia/macrophages in ON lesions. The presence of neurodegeneration in AQP4-deficient regions including myelin-preserved periplaque white matter adjacent the optic nerve plaques and the retina, which is physiologically devoid of myelin, may indicate that demyelination is not necessarily essential for processes of neurodegeneration in NMO.
Conclusion: Severe and widespread neuroaxonal damage with unique dynamics of AQP4 expression on astrocytes/Müller cells and substantial amounts of activated microgila/macrophages were prominent in NMO lesions of the AVP and may be associated with poor recovery in visual function of NMO.
Disclosure:
I. Kawachi has received funding for travel/speaker honoraria or for serving on scientific advisory boards from Novartis, Biogen, Bayer, Mitsubishi Tanabe and Takeda, and research support from a JSPS KAKENHI Grant.
M. Nishizawa has received funding for travel/speaker honoraria from Bayer, Novartis, Otsuka, Genzyme and Kissei, and research support from a Neuroimmunological Disease Research Committee grant from the Ministry of Health, Labor and Welfare, Japan.
M. Hokari, A. Yokoseki, A. Musashi, E. Saji, K. Yanagawa, F. Yanagimura, Y. Toyoshima, A. Kakita, H. Takahashi, and O. Onodera have nothing to disclose.