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Cell. 2016 Jan 14;164(1-2):219-232. doi: 10.1016/j.cell.2015.11.036.

Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.

Author information

1
F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2
F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurosurgery, ChangZheng Hospital, 415 FengYang Road, Shanghai 200003, China.
3
Department of Neurosurgery, ChangZheng Hospital, 415 FengYang Road, Shanghai 200003, China.
4
F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
5
Department of Physiology, Tufts University, Boston, MA 02111, USA.
6
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
7
F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: michela.fagiolini@childrens.harvard.edu.
8
F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: zhigang.he@childrens.harvard.edu.

Abstract

Although a number of repair strategies have been shown to promote axon outgrowth following neuronal injury in the mammalian CNS, it remains unclear whether regenerated axons establish functional synapses and support behavior. Here, in both juvenile and adult mice, we show that either PTEN and SOCS3 co-deletion, or co-overexpression of osteopontin (OPN)/insulin-like growth factor 1 (IGF1)/ciliary neurotrophic factor (CNTF), induces regrowth of retinal axons and formation of functional synapses in the superior colliculus (SC) but not significant recovery of visual function. Further analyses suggest that regenerated axons fail to conduct action potentials from the eye to the SC due to lack of myelination. Consistent with this idea, administration of voltage-gated potassium channel blockers restores conduction and results in increased visual acuity. Thus, enhancing both regeneration and conduction effectively improves function after retinal axon injury.

PMID:
26771493
PMCID:
PMC4863988
DOI:
10.1016/j.cell.2015.11.036
[Indexed for MEDLINE]
Free PMC Article

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