Restoration of Visual Function by Enhancing Conduction in Regenerated Axons

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Axons / drug effects
  • Axons / physiology*
  • Ciliary Neurotrophic Factor / metabolism
  • Electrophysiological Phenomena
  • Eye / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Mice
  • Myelin Sheath / metabolism
  • Optic Nerve
  • Osteopontin / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Potassium Channel Blockers / pharmacology
  • Regeneration / drug effects
  • Superior Colliculi / physiology*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Synapses


  • Ciliary Neurotrophic Factor
  • Potassium Channel Blockers
  • Socs3 protein, mouse
  • Spp1 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • insulin-like growth factor-1, mouse
  • Osteopontin
  • Insulin-Like Growth Factor I
  • 4-Aminopyridine
  • PTEN Phosphohydrolase
  • Pten protein, mouse