Human retinal ganglion cell axon regeneration by recapitulating developmental mechanisms

effects of recruitment of the mTOR pathway

Pooja Teotia, Matthew Van Hook, Dietmar Fischer, Iqbal Ahmad

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalDevelopment (Cambridge, England)
Volume146
Issue number13
DOIs
StatePublished - Jul 4 2019

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Retinal Ganglion Cells
Axons
Regeneration
Central Nervous System
Axotomy
Induced Pluripotent Stem Cells
Microfluidics
Neurogenesis
Wounds and Injuries
Human Development
Glaucoma
Cell Differentiation

Keywords

  • Development
  • Glaucoma
  • RGC
  • Regeneration
  • Retina
  • mTOR

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

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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.",
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