Figure 10.

Optic nerve ultrastructure pathology in the Asah1^P361R/P361R mice. A: Representative micrograph of a normal intraneuronal capillary in the Asah1^+/+ mouse. B and C: Electron micrograph of endothelial cells and pericapillary macrophages with storage vacuoles in Asah1^P361R/P361R mice. D: An astrocyte from an Asah1^+/+ mouse with finely structured cytoplasmic extensions. E and F: Hyperplastic astrocytes from Asah1^P361R/P361R mice with zebra body–like and curved-linear tubular body CTB containing storage vacuoles. Boxed area in E is shown in higher magnification in the inset: Zebra body–like material is presented at higher magnification. G: Normal structured oligodendrocyte from an Asah1^+/+ mouse. H and I: Oligodendrocytes containing zebra body–like storage bodies in cytoplasm. J: Micrograph displaying ON axon diameters and axonal density in Asah1^+/+ mice. Asah1^P361R/P361R mice appear to show less density in ON axons. K and L: Presence of neuronal axonal dystrophy (axonal spheroid) containing accumulated axonal cargo (K; highlighted by black boxed area and enlarged in L). Double dagger denotes capillary lumina; white asterisk, astrocyte; black asterisk, astrocyte nucleus; white dagger, endothelial cell nucleus; black dagger, macrophage nucleus; section symbol, oligodendrocyte nucleus; black arrows, zebra body–like storage bodies; white arrow, storage vacuole with curvilinear tubular (Farber) bodies; white arrowheads, partly cleared macrophage storage vacuoles with curvilinear tubular (Farber) bodies; black arrowheads, outline of the axonal spheroid. The G-ratio (axon diameter/fiber diameter) was plotted against axon diameter. M: In samples from 8- to 9-week–old animals, Asah1^P361R/P361R mice (1350 axons) show a difference in myelination compared with Asah1^+/+ mice (1333 axons) (P < 0.001 from clustered rank sum test). N: Comparison of axon diameters. O and P: Quantification of myelinated axon density and percentage of myelinated axons. n = 3 (M). ^∗∗∗P < 0.001. Scale bar = 2 μm (A–L).