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Roles of Treg/Th17 Cell Imbalance and Neuronal Damage in the Visual Dysfunction Observed in Experimental Autoimmune Optic Neuritis Chronologically

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Abstract

Optic neuritis associated with multiple sclerosis and its animal model, experimental autoimmune optic neuritis (EAON), is characterized by inflammation, T cell activation, demyelination, and neuronal damage, which might induce permanent vision loss. Elucidating the chronological relationship among the features is critical for treatment of demyelinating optic neuritis. EAON was induced in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein subcutaneously, and visual function was assessed by flash-visual evoked potential (F-VEP) at days 7, 11, 14, 19, 23, 28 post-immunization. Retinal ganglion cell (RGC) apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick-end labeling. Demyelination and axonal damage were verified with myelin basic protein (MBP) and β-amyloid precursor protein staining, respectively. Real-time polymerase chain reaction quantified IL-17, IL-1β, TGF-β, FoxP3, IL-6, and IL-10 mRNA expression in the optic nerve, as well as FoxP3 and IL-17 staining. Systemic changes of Th17 and Treg cells were tested by flow cytometry in spleen. F-VEP latency was prolonged at 11 days and peaked at 23 days commensurate with demyelination. However, F-VEP amplitude was reduced at 11 days, preceding axon damage, and was exacerbated at 23 days when a peak in RGC apoptosis was detected. Th17 cells up-regulated as early as 7 days and peaked at 11 days, while Treg cells down-regulated inversely compared to Th17 cells change as verified by IL-17 and FoxP3 expression; spleen cell samples were slightly different, demonstrating marked changed at 14 days. Treg/Th17 cell imbalance in the optic nerve precedes and may initiate neuronal damage of axons and RGCs. These changes are commensurate with the appearances of visual dysfunction reflected in F-VEP and hence may offer a novel therapeutic avenue for vision preservation.

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Acknowledgments

This study was supported by Natural Science Foundation of Tianjin grant (Grant Numbers 12JCYBJC33900 and 14JCYBJC28000) and National Natural Science Foundation of China (Grant Numbers 81371038 and 91442124).

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Authors and Affiliations

  1. Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin, 300052, China

    Yuanyuan Liu, Caiyun You, Zhuhong Zhang, Jingkai Zhang & Hua Yan

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  1. Yuanyuan Liu
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  2. Caiyun You
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Correspondence to Hua Yan.

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Liu, Y., You, C., Zhang, Z. et al. Roles of Treg/Th17 Cell Imbalance and Neuronal Damage in the Visual Dysfunction Observed in Experimental Autoimmune Optic Neuritis Chronologically. Neuromol Med 17, 391–403 (2015). https://doi.org/10.1007/s12017-015-8368-4

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