Nonneuronal control of the differential distribution of myelin along retinal ganglion cell axons in the mouse

TY - JOUR

T1 - Nonneuronal control of the differential distribution of myelin along retinal ganglion cell axons in the mouse

AU - Yang, Xiaoli

AU - Zou, Haidong

AU - Jung, Gila

AU - Richard, Gisbert

AU - Linke, Stephan J

AU - Ader, Marius

AU - Bartsch, Udo

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

KW - Animals

KW - Animals, Newborn

KW - Axons

KW - Cell Differentiation

KW - Cells, Cultured

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Mice

KW - Mice, Inbred C57BL

KW - Microscopy, Electron

KW - Myelin Sheath

KW - Retinal Ganglion Cells

KW - Stem Cell Transplantation

U2 - 10.1167/iovs.13-12596

DO - 10.1167/iovs.13-12596

M3 - SCORING: Journal article

C2 - 24222305

VL - 54

SP - 7819

EP - 7827

JO - INVEST OPHTH VIS SCI

JF - INVEST OPHTH VIS SCI

SN - 0146-0404

IS - 13

ER -