Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state

J Neurosci. 2004 Feb 18;24(7):1646-51. doi: 10.1523/JNEUROSCI.5119-03.2004.


Mature retinal ganglion cells (RGCs), like other CNS neurons, cannot regrow injured axons into a myelin-rich environment. If stimulated by macrophage-derived factors, however, RGCs can regenerate their axons for considerable distances through the distal optic nerve. Using this "sensitized background," we investigated the effects of either increasing the expression or suppressing the activity of the Nogo receptor (NgR). NgR mediates the growth-inhibiting effects of three myelin proteins, Nogo, OMgp (oligodendrocyte-myelin glycoprotein), and MAG (myelin-associated glycoprotein). Transfecting growth-sensitized RGCs with adeno-associated viruses expressing a dominant-negative form of NgR (NgR(DN)) increased axon regeneration several-fold; however, when the growth program of RGCs was not activated, NgR(DN) expression had no beneficial effects. Overexpression of wild-type NgR blocked almost all regeneration from growth-sensitized RGCs and caused axons proximal to the lesion site to retract. We conclude that gene therapy is an effective approach to enhancing axon regeneration in the CNS and that inactivation of NgR functioning greatly enhances axon regeneration provided the intrinsic growth program of neurons is activated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Survival / genetics
  • Culture Techniques
  • Dependovirus / genetics
  • Female
  • GPI-Linked Proteins
  • Genes, Dominant
  • Genes, Reporter
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Myelin Proteins
  • Nerve Crush
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Nogo Receptor 1
  • Optic Nerve / drug effects*
  • Optic Nerve / growth & development
  • Optic Nerve Injuries / drug therapy*
  • Optic Nerve Injuries / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface
  • Receptors, Peptide / antagonists & inhibitors*
  • Receptors, Peptide / genetics
  • Receptors, Peptide / physiology
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / physiology*
  • Time Factors
  • Transfection


  • GPI-Linked Proteins
  • Luminescent Proteins
  • Myelin Proteins
  • Nogo Receptor 1
  • Receptors, Cell Surface
  • Receptors, Peptide
  • Rtn4r protein, rat
  • Green Fluorescent Proteins