Fig. 3

PS19 mice treated with 51657 had significantly increased ON MT density and reduced axonal dystrophy. ON sections from vehicle-treated WT mice (n = 10) and PS19 mice treated with vehicle (n = 9) or 3 mg/kg (n = 8) or 10 mg/kg (n = 10) of 51657 were imaged by EM, and the number of MTs and dystrophic axons within treatment-masked images were counted as previously described [25]. a Quantification of MT density in ON sections demonstrates that vehicle-treated PS19 mice have a MT deficit relative to vehicle-treated WT mice, and treatment of PS19 mice with 3 mg/kg or 10 mg/kg of 51657 increases MT density to a level comparable to that of WT mice. b Quantification of ON EM images reveals a significant reduction in axonal dystrophy in PS19 mice receiving either 3 mg/kg or 10 mg/kg of 51657 compared to vehicle-treated PS19 mice. After quantification, a Grubb’s test determined there was an extreme outlier within the 10 mg/kg 51657 group that was not used for quantification. Analyses consisted of a one-way ANOVA with Tukey’s post-hoc analysis of between group differences. Error bars represent SEM. c Representative ON images from a vehicle-treated WT and PS19 mouse, with example MTs indicated by arrows. As depicted in the PS19 vehicle image, hexagonal fields of 0.035 μm² were overlaid on the ON images, with MTs counted within the hexagon and on three of the six borders to avoid repeat counting of MTs of MTs on adjacent hexagons (see also [27]). Scale bar represents 0.5 μM. d Representative ON images from a vehicle-treated WT and PS19 mouse, as well as a PS19 mouse that received a twice-weekly dose of 10 mg/kg of 51657. Vehicle-treated PS19 mice have greater axonal dystrophy, as evidenced by fewer intact axons and more axons that are demyelinated or debris-filled, than vehicle-treated WT mice. ONs of PS19 mice treated with 51657 more closely resembled those of vehicle-treated WT mice. Scale bar = 2 μm