Sun Li, Weng Huan, Li Zhenxin
Department of Ophthalmology, Huashan Hospital, Fudan University Shanghai, China.
Department of Neurology, Huashan Hospital, Fudan University Shanghai, China.
Int J Clin Exp Pathol. 2015 Dec 1;8(12):15749-58. eCollection 2015.
Idiopathic optic neuritis (ION) is an inflammation of the optic nerve that may result in a complete or partial loss of vision. ION is usually due to the immune attack of the myelin sheath covering the optic nerve. ION acts frequently as the first symptoms of multiple sclerosis (MS) and neuromyelitis optica (NMO), or other inflammatory demyelinating disorders. The pathogenic progression of ION remains unclear. Experimental autoimmune encephalitis (EAE) is a commonly used model of idiopathic inflammatory demyelinating disorders (IIDDs); the optic nerve is affected in EAE as well. The specific mediators of demyelination in optic neuritis are unknown. Recent studies have indicated what T-cell activation in peripheral blood is associated with optic neuritis pathogenesis. The object of the present study was to determine whether certain cytokines (IL-6, IL-17A, and IL-23) and AQP4 contribute to the demyelinating process using EAE model. We have found that IL-6R, AQP4 and IL-23R are significantly increased in mRNA and protein levels in optic nerves in EAE mice compared to control mice; serum AQP4, IL-6, IL-17A, IL-23 are increased whereas transforming growth factor beta (TGF-β) is decreased in EAE mice. These results suggest that AQP4 and selective cytokines in serum are associated with ION pathogenesis in the animal model, and these results shine light for future clinical diagnosis as potential biomarkers in ION patients.
特发性视神经炎(ION)是一种视神经炎症,可能导致视力完全或部分丧失。ION通常是由于覆盖视神经的髓鞘受到免疫攻击所致。ION常作为多发性硬化症(MS)和视神经脊髓炎(NMO)或其他炎性脱髓鞘疾病的首发症状。ION的致病进展尚不清楚。实验性自身免疫性脑脊髓炎(EAE)是一种常用的特发性炎性脱髓鞘疾病(IIDDs)模型;视神经在EAE中也会受到影响。视神经炎中脱髓鞘的具体介质尚不清楚。最近的研究表明外周血中的T细胞活化与视神经炎发病机制有关。本研究的目的是使用EAE模型确定某些细胞因子(IL-6、IL-17A和IL-23)和水通道蛋白4(AQP4)是否参与脱髓鞘过程。我们发现,与对照小鼠相比,EAE小鼠视神经中IL-6R、AQP4和IL-23R的mRNA和蛋白水平显著升高;EAE小鼠血清中的AQP4、IL-6、IL-17A、IL-23升高,而转化生长因子β(TGF-β)降低。这些结果表明,血清中的AQP4和选择性细胞因子与动物模型中ION的发病机制有关,这些结果为未来作为ION患者潜在生物标志物的临床诊断提供了线索。