Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway

Neuropharmacology. 2012 Nov;63(6):1182-90. doi: 10.1016/j.neuropharm.2012.06.037. Epub 2012 Jun 29.


We investigated whether the RhoA/ROCK pathway was involved in the effect of erythropoietin (EPO) to promote retinal ganglion cells (RGCs) axonal regeneration in a rat optic nerve crush (ONC) model. We demonstrated that both EPO and ROCK inhibitor Y-27632 significantly enhanced RGCs survival and axon regeneration in vivo, and the effects of these agents were additive. Expression of active-RhoA was decreased after EPO or Y-27632 per pull down assay and affinity precipitation. Administration of EPO and Y-27632 cocktail resulted in even more RhoA inactivation, decreased expression of ROCK-1 and ROCK-2, and increased expression of growth associated protein-43 (GAP-43) protein per immunohistochemistry and western blot analysis. Down-regulation of active-RhoA, ROCK-1, and ROCK-2 expression by EPO coincided with the appearance of larger numbers of regenerating axons. In conclusion, the RhoA/ROCK signaling pathway was involved in the EPO effect to promote RGCs axon regeneration after ONC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Animals
  • Axons / drug effects*
  • Blotting, Western
  • Cell Survival / drug effects
  • Enzyme Inhibitors / pharmacology
  • Erythropoietin / pharmacology*
  • GAP-43 Protein / biosynthesis
  • GAP-43 Protein / genetics
  • Immunohistochemistry
  • Male
  • Nerve Crush
  • Nerve Regeneration / drug effects*
  • Optic Nerve / cytology*
  • Optic Nerve / growth & development*
  • Optic Nerve Injuries / pathology*
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Superior Colliculi / cytology
  • Superior Colliculi / drug effects
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / physiology*
  • rhoA GTP-Binding Protein / physiology*


  • Amides
  • Enzyme Inhibitors
  • GAP-43 Protein
  • Pyridines
  • Erythropoietin
  • Y 27632
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein