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    The optic nerve lamina region is a neural progenitor cell niche

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    Author
    Bernstein, S L
    Guo, Y
    Kerr, C
    Fawcett, R J
    Stern, J H
    Temple, S
    Mehrabian, Z
    Date
    2020-07-28
    Journal
    Proceedings of the National Academy of Sciences of the United States of America (PNAS)
    Publisher
    National Academy of Sciences
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1073/pnas.2001858117
    Abstract
    Retinal ganglion cell axons forming the optic nerve (ON) emerge unmyelinated from the eye and become myelinated after passage through the optic nerve lamina region (ONLR), a transitional area containing a vascular plexus. The ONLR has a number of unusual characteristics: it inhibits intraocular myelination, enables postnatal ON myelination of growing axons, modulates the fluid pressure differences between eye and brain, and is the primary lesion site in the age-related disease open angle glaucoma (OAG). We demonstrate that the human and rodent ONLR possesses a mitotically active, age-depletable neural progenitor cell (NPC) niche, with unique characteristics and culture requirements. These NPCs generate both forms of macroglia: astrocytes and oligodendrocytes, and can form neurospheres in culture. Using reporter mice with SOX2-driven, inducible gene expression, we show that ONLR-NPCs generate macroglial cells for the anterior ON. Early ONLR-NPC loss results in regional dysfunction and hypomyelination. In adulthood, ONLR-NPCs may enable glial replacement and remyelination. ONLR-NPC depletion may help explain why ON diseases such as OAG progress in severity during aging.
    Keyword
    eye
    lamina
    neural progenitor cell niche
    optic nerve
    postnatal axon growth
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13476
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.2001858117
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