Purpose: In most mammalian species, retinal ganglion cell (RGC) axons are myelinated in the optic nerve, but remain nonmyelinated in the retinal nerve fiber layer and the most proximal (i.e., retina-near) region of the nerve. Here we analyzed whether RGCs are involved in the control of this characteristic distribution of oligodendrocytes and myelin in the primary visual pathway of mice.
Methods: Neurospheres were enriched in oligodendrocyte progenitor cells (OPCs) by a short-term exposure to platelet-derived growth factor (PDGF) and grafted into the retina of young postnatal mice close to the optic disc. Immunohistochemistry was performed to study the integration and differentiation of the grafted cells, and the formation of donor-derived myelin in the normally nonmyelinated retinal nerve fiber layer and intrabulbar and most proximal retrobulbar region of the optic nerve.
Results: Intraretinal transplantations of small-sized PDGF-treated neurospheres into young postnatal mice resulted in extensive integration of the grafted cells into host retinas. A significant fraction of the donor cells differentiated into oligodendrocytes that myelinated the nerve fiber layer. Importantly, RGC axon segments within the normally nonmyelinated intrabulbar and most proximal retrobulbar region of the nerve also became myelinated in a fraction of animals.
Conclusions: This is the first report demonstrating that the normally nonmyelinated intrabulbar and retrobulbar segments of RGC axons are competent to become myelinated. Results support the view that the differential distribution of myelin and oligodendrocytes in the primary visual pathway is controlled by nonneuronal factors rather than by the RGCs themselves.
Keywords: myelination; neurosphere cultures; oligodendrocytes; retina; transplantation.