The capacity of the human central nervous system to regenerate after injury or illness is limited, and the resulting functional impairments carry a wide societal and personal burden. Glaucoma is one prevalent example: degeneration of the retinal ganglion cells (RGCs) – the axons of which form the optic nerve connecting the retina to the brain – leads to permanent blindness. Previous work using rodent models has found the mTOR pathway promotes RGC axonal development and regeneration, but it has been unclear whether it also does so in humans, an issue now addressed by Iqbal Ahmad and colleagues. They first find that mTOR activity is high in rat retinal development but reduces once cells reach maturity, and see a similar pattern in RNAseq data from human development. Activation of the mTOR pathway stimulated RGC differentiation from human induced pluripotent stem cells (and also from rat retinal progenitor cells). Differentiated human RGCs show neurite elaboration, recruitment of growth regulatory factors, growth cone guidance and functional maturation, in a manner facilitated by mTOR pathway activation. Finally, the mTOR pathway promotes human RGC axon regeneration following axotomy in a microfluidic chamber system, and the mTOR and JAK-STAT3 pathways independently and additively promote regeneration. Regeneration therefore recapitulates development in the human optic nerve, and mTOR is a promising therapeutic target for glaucoma.
RGCing the light with help from mTOR
RGCing the light with help from mTOR. Development 1 July 2019; 146 (13): e1303. doi:
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