Fig. 4.

Spatial distribution of demyelination and remyelination in the ON during active disease and after recovery. (A) Schematic image of the ON: quantification and color coding strategy used to identify areas of demyelination and remyelination. Each ON was cut and labeled from 1 to 5 from the chiasm to retina. All areas of ON were scored for remyelination and demyelination and scores were replaced with red and yellow dots representing remyelination and demyelination, respectively. (B) Myelin status along the ON during active disease and after recovery showing distribution of demyelination and remyelination. In active disease, the ON is demyelinated in both the core and subpia, and then remyelination starts from subpia extending to the core at the retinal end of the nerve. On recovery, the entire nerve is fully remyelinated. Red and yellow dots represent remyelination and demyelination, respectively. (C–F) The majority of axons of all calibers are demyelinated in the core, proximal to the chiasm (levels 1 and 3), while small- and medium-caliber axons are the first axons remyelinated in the subpia. In contrast, most of the axons in the core proximal to the retina (level 5) are remyelinated. (G) Table shows the percentage of demyelinated and remyelinated axons of different sizes in D and E. (H and I) The ON at level 3 during active disease and after recovery showing g-ratio measurement in all areas across the ON. (Scale bar in C–F: 20 µm.)