ABSTRACT
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 model 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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: I.A.; Methodology: P.T., M.J.V.H., I.A.; Software: P.T.; Validation: D.F., I.A.; Formal analysis: P.T., M.J.V.H., D.F., I.A.; Investigation: P.T., M.J.V.H., D.F.; Resources: D.F.; Data curation: P.T., I.A.; Writing - original draft: P.T., I.A.; Visualization: I.A.; Supervision: I.A.; Project administration: I.A.; Funding acquisition: I.A.
Funding
This research was supported by the National Eye Institute (2R01EY022051) and Nebraska Department of Health and Human Services (LB606). Deposited in PMC for release after 12 months.
Supplementary information
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.178012.supplemental
- Received March 12, 2019.
- Accepted May 15, 2019.
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