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. 2021 Mar 21;3(2):fcab047. doi: 10.1093/braincomms/fcab047

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© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Treatment effects of fingolimod and teriflunomide are predominantly immunomodulatory. (A) Representative light microscopy and quantification of SMI32+ axonal spheroids in optic nerves and (B), immune fluorescence microscopy and quantification of RBPMS+ retinal ganglion cells in retinae from 7-month-old Ppt1^+/+, Ppt1⁻^/⁻Rag1⁻^/⁻, fingolimod-treated Ppt1⁻^/⁻Rag1⁻^/⁻ (+ FTY720) and teriflunomide-treated Ppt1⁻^/⁻Rag1⁻^/⁻ (+ Teriflunomide) mice (circle = mean value of one mouse; n = 4 mice per group, one-way ANOVA and Tukey’s post hoc test). Scale bars: 20 µm. (C) Representative peripapillary OCT circle scans at 7 months and longitudinal analysis of NFL/GCL/IPL thickness (n = 4 mice per group, one-way ANOVA and Tukey’s post hoc test). (D) Total brain weights of 7-month-old Ppt1^+/+, Ppt1⁻^/⁻Rag1⁻^/⁻, fingolimod-treated Ppt1⁻^/⁻Rag1⁻^/⁻ and teriflunomide-treated Ppt1⁻^/⁻Rag1⁻^/⁻ mice (n = 4 mice per group, one-way ANOVA and Tukey’s post hoc test). (E) Quantification of myoclonic jerks in 7-month-old Ppt1^+/+, Ppt1⁻^/⁻Rag1⁻^/⁻, fingolimod-treated Ppt1⁻^/⁻Rag1⁻^/⁻ and teriflunomide-treated Ppt1⁻^/⁻Rag1⁻^/⁻ mice (circle = mean value of one mouse; n = 4 mice per group, one-way ANOVA and Tukey’s post hoc test). (F) Longitudinal analysis of cumulative Rotarod performance (circle = mean value of five consecutive runs of one mouse n = 4 mice per group, two-way ANOVA and Tukey’s post hoc test). Note that none of the investigated parameters was further improved by either of the immunomodulators in comparison to untreated Ppt1⁻^/⁻Rag1⁻^/⁻ mice. Grey horizontal lines in all graphs indicate mean values of immune competent Ppt1⁻^/⁻Rag1^+/+ mice. *P < 0.05, **P < 0.01, ***P < 0.001.