Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Exp Eye Res. 2014 Feb;119:61-9. doi: 10.1016/j.exer.2013.12.010. Epub 2013 Dec 24.
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.
视神经脊髓炎（NMO）是一种主要靶向视神经和脊髓的自身免疫性炎症性神经退行性疾病。水通道蛋白 4（AQP4）的自身抗体，该蛋白在星形胶质细胞的足突表达，与 NMO 的发病机制有关。我们评估了 NMO 谱障碍（NMOSD）血清阳性患者的血清对啮齿动物视神经和视网膜的影响。血清取自血清阳性 NMOSD（AQP4+）、血清阴性特发性视神经炎（AQP4-）和健康志愿者（对照）患者。通过之前建立的基于细胞的测定法测量血清中的抗 AQP4 抗体。将患者的血清在去鞘后应用于视神经。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 和神经胶质纤维酸性蛋白的表达。此外，在 AQP4+血清处理的视神经中观察到人类 IgG 免疫反应和炎症细胞的明显浸润。治疗后 14 天，神经丝的免疫反应性降低，而不是 7 天。实时聚合酶链反应显示，暴露于 AQP4+血清的眼睛的视网膜中的神经丝基因表达减少。视网膜 flatmount 上的逆行氟金标记显示，当应用 AQP4+血清时，视网膜节细胞的数量显著减少。本模型表明，血清阳性 NMOSD 患者的血清导致视神经中区域性星形胶质细胞变性和炎症细胞浸润，最终导致损伤部位以外区域的 RGCs 及其轴突丧失。
