Sera from patients with seropositive neuromyelitis optica spectral disorders caused the degeneration of rodent optic nerve
Sera from patients with seropositive neuromyelitis optica spectral disorders caused the degeneration of rodent optic nerve
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DOI：
10.1016/j.exer.2013.12.010
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发表时间：
2014-02-01
影响因子：
3.4
通讯作者：
Negi, Akira
中科院分区：
文献类型：
--
作者：
Matsumoto, Yoshiko;Kanamori, Akiyasu;Negi, Akira
视神经肌萎缩症（NMO）是一种主要针对视神经和脊髓的自身免疫性炎症性神经破坏性疾病。针对水通道蛋白水通道蛋白4（AQP4）的自身抗体在NMO的发病机制中有牵连，所述水通道蛋白水通道蛋白4表达于星形胶质细胞的内足。我们评估血清阳性患者的血清与NMO频谱障碍（NMOSDs）的啮齿动物视神经和视网膜的影响。从血清阳性NMOSD患者（AQP4+）、血清阴性特发性视神经炎患者（AQP4）和健康志愿者（对照）中获得血清。通过先前建立的基于细胞的测定来测量血清中的抗AQP4抗体。将患者血清涂于脱鞘后的视神经上。免疫组化显示，在治疗后7天，暴露于AQP4+血清的视神经区域失去了AQP4和胶质细胞酸性蛋白的表达。此外，在用AQP4+血清处理的视神经中观察到人IgG免疫反应性和炎症细胞的显著侵入。神经丝的免疫反应性在治疗后14天降低，而不是7天。实时聚合酶链反应显示，在14天暴露于AQP4+血清的眼睛视网膜中神经丝的基因表达减少。逆行荧光金标记的视网膜flatmount揭示了显着减少的视网膜神经节细胞的数量时，AQP4+血清的应用。本模型已经证明，来自具有血清阳性NMOSD的患者的血清导致视神经中的区域星形胶质细胞变性和炎性细胞侵袭，导致在损伤部位以外的区域的RGC及其轴突的最终损失。皇冠版权所有（C）2013由爱思唯尔有限公司出版。保留所有权利。
Neuromyelitis optica (NMO) is an autoimmune inflammatory, neurodestructive disease primarily targeting the optic nerve and spinal cord. An autoantibody against water channel protein aquaporin-4 (AQP4), which is expressed at endofeet of astrocytes has been implicated in the pathogenesis of NMO. We evaluated the impact of sera of seropositive patients with NMO spectrum disorders (NMOSDs) on the rodent optic nerve and retina. Serum was obtained either from patients with seropositive NMOSD (AQP4+), seronegative patient with idiopathic optic neuritis (AQP4), and healthy volunteers (control). Anti-AQP4 antibody in a serum was measured by a previously established cell-based assay. The patients' sera were applied on the optic nerve after de-sheathed. Immunohistochemistry showed that at 7 days after the treatment, the area of the optic nerve exposed to the AQP4+ sera lost expression of both AQP4 and glial fibrillary acidic protein. Also, Human-IgG immunoreactivity and marked invasion of inflammation cells were observed in the optic nerve treated with AQP4+ serum. Immnoreactivity of neurofilament was reduced at 14 days after the treatment, not 7 days. Real-time polymerase chain reaction revealed the reduced gene expression of neurofilament in retina from the eye that was exposed to the AQP4+ sera at 14 days. Retrograde fluorogold-labeling on the retinal flatmount disclosed the significantly reduced number of retinal ganglion cells when the AQP4+ sera were applied. The present model has demonstrated that the sera from patients with seropositive NMOSDs led to the regional astrocytic degeneration and inflammatory cell invasion in the optic nerve, resulting in the ultimate loss of RGCs and their axons at areas beyond the injury site. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.