Larabee Chelsea M, Hu Yang, Desai Shruti, Georgescu Constantin, Wren Jonathan D, Axtell Robert C, Plafker Scott M
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Mol Vis. 2016 Apr 11;22:332-41. eCollection 2016.
Optic neuritis affects most patients with multiple sclerosis (MS), and current treatments are unreliable. The purpose of this study was to characterize the contribution of Th1 and Th17 cells to the development of optic neuritis.
Mice were passively transferred myelin-specific Th1 or Th17 cells to induce experimental autoimmune encephalomyelitis (EAE), a model of neuroautoimmunity. Visual acuity was assessed daily with optokinetic tracking, and 1, 2, and 3 weeks post-induction, optic nerves and retinas were harvested for immunohistochemical analyses.
Passive transfer experimental autoimmune encephalomyelitis elicits acute episodes of asymmetric visual deficits and is exacerbated in Th17-EAE relative to Th1-EAE. The Th17-EAE optic nerves contained more inflammatory infiltrates and an increased neutrophil to macrophage ratio. Significant geographic degeneration of the retinal ganglion cells accompanied Th17-EAE but not Th1.
Th17-induced transfer EAE recapitulates pathologies observed in MS-associated optic neuritis, namely, monocular episodes of vision loss, optic nerve inflammation, and geographic retinal ganglion cell (RGC) degeneration.
视神经炎影响大多数多发性硬化症（MS）患者，且目前的治疗方法不可靠。本研究的目的是明确Th1和Th17细胞在视神经炎发病过程中的作用。
将髓鞘特异性Th1或Th17细胞被动转移至小鼠体内，以诱导实验性自身免疫性脑脊髓炎（EAE），这是一种神经自身免疫模型。每天用视动跟踪法评估视力，在诱导后1、2和3周，采集视神经和视网膜进行免疫组织化学分析。
被动转移实验性自身免疫性脑脊髓炎引发不对称视力缺陷的急性发作，且相对于Th1-EAE，Th17-EAE病情更严重。Th17-EAE的视神经中有更多炎性浸润，中性粒细胞与巨噬细胞的比例增加。视网膜神经节细胞出现明显的地图状变性，这与Th17-EAE有关，而与Th1无关。
Th17诱导的转移型EAE重现了MS相关性视神经炎中观察到的病理特征，即单眼视力丧失、视神经炎症和视网膜神经节细胞（RGC）地图状变性。
