Caprine beta-mannosidosis: development of glial and myelin abnormalities in optic nerve and corpus callosum

In caprine beta-mannosidosis, an inherited dysmyelinating disorder, the myelin deficit shows substantial variation throughout the nervous system. In this study morphometric analysis of optic nerve and corpus callosum sections at selected developmental stages was conducted in order to investigate development and persistence of myelin sheaths, the population of axons ensheathed, and the extent of myelin deficits and glial cell abnormalities. The results show that the myelin deficit is severe at very early stages of development and persists to about the same extent into postnatal life. The corpus callosum, much more severely involved than the optic nerve, contains a substantially smaller percentage of myelinated axons when compared to control. In both regions, larger axons are preferentially myelinated. In the corpus callosum before myelination begins, many glial cells appear abnormal, suggesting an early cellular defect. In the postnatal, myelin-deficient corpus callosum, there is a substantial decrease in glial cell density as compared to control, with abnormal appearance of many of the remaining cell profiles. These results define developmental characteristics of the dysmyelination in caprine beta-mannosidosis and document both the early appearance and the persistence of glial cell body and myelin abnormalities.