DIRECT OBSERVATION OF MYELINATION IN-VIVO IN THE MATURE HUMAN CENTRAL-NERVOUS-SYSTEM - A MODEL FOR THE BEHAVIOR 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 analys ed the position, area and thickness of the nerve-fibre layer in 60 pat ches 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, a nd volumes of myelinated tissue were then estimated for each patch. Re tinal myelination occurred in three patterns: thick patches contiguous with the optic disc (type I); thin, striated patches detached from th e disc (type II); or massive myelination of the posterior pole associa ted with severe amblyopia (type III). The papillomacular bundle did no r myelinate in types I and II and was relatively spared in type III pa tches, suggesting that migratory oligodendrocyte progenitors are not s upported by these axons. The local nerve-fibre layer determined parch size, and quantal myelination was evident with modal peaks of patch vo lume at 0.16 and 0.64 mm(3). Myelination advanced at patch edges when observed over time, consistent with the hypothesis that new oligodendr ocytes are produced in adulthood. We propose a theoretical model where patches of retinal myelination are the clonal progeny of a few oligod endrocyte progenitors exhibiting two different behaviours. First, a hi ghly migratory, nonmyelinating progenitor uses larger phylogenetically older axons as the substrate for movement. Secondly, a more mature pr ogenitor generates myelinating oligodendrocytes well into adult life, but traverses only short distances. Using this data, we can estimate t he number of oligodendrocytes in these clones and population doubling- time. This study supports a role for axon-derived signals in the regul ation of human oligodendrocyte progenitor behaviour and myelination in vivo.