Human retinal ganglion cell axon regeneration by recapitulating developmental mechanisms: effects of recruitment of the mTOR pathway
| Autor: | Pooja Teotia, Iqbal Ahmad, Matthew J. Van Hook, Dietmar Fischer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Retinal Ganglion Cells genetic structures medicine.medical_treatment Human Development Embryonic Development Biology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Pregnancy medicine Animals Humans Axon Induced pluripotent stem cell Molecular Biology PI3K/AKT/mTOR pathway Cells Cultured 030304 developmental biology 0303 health sciences Retina Regeneration (biology) TOR Serine-Threonine Kinases Neurogenesis Gene Expression Regulation Developmental Cell Differentiation Embryo Mammalian eye diseases Axons Nerve Regeneration Rats medicine.anatomical_structure Retinal ganglion cell Female sense organs Axotomy Neuroscience 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Zdroj: | Development |
| ISSN: | 1477-9129 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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