Direct observation of myelination in vivo in the mature human central nervous system. A model for the behaviour of oligodendrocyte progenitors and their progeny.

We studied patches of CNS myelin in human retina in vivo to determine the pattern of myelination and the local influence of axons. We analysed the position, area and thickness of the nerve-fibre layer in 60 patches of retinal myelin in 47 eyes (in 37 adults and two adolescents). Five patches in four eyes were studied serially over 6-11 years. Nerve-fibre layer thickness was obtained from an atlas of primate retina, and volumes of myelinated tissue were then estimated for each patch. Retinal myelination occurred in three patterns: thick patches contiguous with the optic disc (type I); thin, striated patches detached from the disc (type II); or massive myelination of the posterior pole associated with severe amblyopia (type III). The papillomacular bundle did not myelinate in types I and II and was relatively spared in type III patches, suggesting that migratory oligodendrocyte progenitors are not supported by these axons. The local nerve-fibre layer determined patch size, and quantal myelination was evident with modal peaks of patch volume at 0.16 and 0.64 mm3. Myelination advanced at patch edges when observed over time, consistent with the hypothesis that new oligodendrocytes are produced in adulthood. We propose a theoretical model where patches of retinal myelination are the clonal progeny of a few oligodendrocyte progenitors exhibiting two different behaviours. First, a highly migratory, nonmyelinating progenitor uses larger, phylogenetically older axons as the substrate for movement. Secondly, a more mature progenitor generates myelinating oligodendrocytes well into adult life, but traverses only short distances. Using this data, we can estimate the number of oligodendrocytes in these clones and population doubling-time. This study supports a role for axon-derived signals in the regulation of human oligodendrocyte progenitor behaviour and myelination in vivo.