Raf-1 Kinase Inhibitory Protein (RKIP) Promotes Retinal Ganglion Cell Survival and Axonal Regeneration Following Optic Nerve Crush

J Mol Neurosci. 2015 Oct;57(2):243-8. doi: 10.1007/s12031-015-0612-8. Epub 2015 Jul 10.

Abstract

Raf-1 kinase inhibitory protein (RKIP), a member of the phosphatidylethanolamine-binding protein (PEBP) family, plays an important role in neuronal apoptosis and cognitive deficits associated with neurodegenerative diseases. However, the biological function of RKIP in the retina is still unclear. Therefore, in the present study, we investigated the expression of RKIP in mouse retina following optic nerve crush (ONC) and evaluated the effects of RKIP on retinal ganglion cells (RGCs) apoptosis and axonal regeneration after ONC. Our results showed that the expression of RKIP was markedly decreased in the injured retina. Overexpression of RKIP inhibits RGC apoptosis and promotes axonal regeneration after ONC. Furthermore, overexpression of RKIP significantly increased the phosphorylation in extracellular signal-related kinase (ERK)1/2 and AKT in the injured retina. Taken together, these results suggest that RKIP promotes RGCs survival and axonal regeneration following ONC through promoting the ERK signaling pathway, implying that RKIP may serve as a potential molecular target for the treatment of glaucoma.

Keywords: Axonal regeneration; Optic nerve crush; Raf-1 kinase inhibitory protein (RKIP); Retinal ganglion cells (RGCs).

MeSH terms

  • Animals
  • Apoptosis
  • Axons / metabolism*
  • Axons / physiology
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nerve Regeneration*
  • Optic Nerve Injuries / metabolism*
  • Phosphatidylethanolamine Binding Protein / genetics
  • Phosphatidylethanolamine Binding Protein / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / physiology

Substances

  • Phosphatidylethanolamine Binding Protein
  • Raf kinase inhibitory protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3