Journal
DEVELOPMENT
Volume 146, Issue 13, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.178012
Keywords
Regeneration; Retina; mTOR; Development; RGC; Glaucoma
Categories
Funding
- National Eye Institute [2R01EY022051]
- Nebraska Department of Health and Human Services [LB606]
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The poor axon regeneration in the central nervous system (CNS) often leads to permanent functional deficit following disease or injury. For example, degeneration of retinal ganglion cell (RGC) axons in glaucoma leads to irreversible loss of vision. Here, we have tested the hypothesis that the mTOR pathway regulates the development of human RGCs and that its recruitment after injury facilitates axon regeneration. We observed that the mTOR pathway is active during RGC differentiation, and using the induced pluripotent stem cell mod& of neurogenesis show that it facilitates the differentiation, function and neuritogenesis of human RGCs. Using a microfluidic model, we demonstrate that recruitment of the mTOR pathway facilitates human RGC axon regeneration after axotomy, providing evidence that the recapitulation of developmental mechanism(s) might be a viable approach for facilitating axon regeneration in the diseased or injured human CNS, thus helping to reduce and/or recover loss of function.
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