EphA5 and ephrin-A2 expression during optic nerve regeneration: a 'two-edged sword'

Eur J Neurosci. 2007 Feb;25(3):744-52. doi: 10.1111/j.1460-9568.2007.05321.x.

Abstract

During development, gradients of EphA receptors (nasal(low)-temporal(high)) and their ligands ephrin-As (rostral(low)-caudal(high)) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5-expressing RGC axons are repulsed by ephrin-A2-expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but ephrin-A2 expression is down-regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded; by contrast, SC ephrin-A2 is up-regulated to a rostral(low)-caudal(high) gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasal(low)-temporal(high) EphA5 gradient in RGCs and establishment of a rostral(low)-caudal(high) ephrin-A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high ephrin-A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive ephrin-A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Axotomy
  • Cell Survival / physiology
  • Ephrin-A2 / genetics*
  • Ephrin-A2 / metabolism
  • Ephrin-A5 / genetics*
  • Ephrin-A5 / metabolism
  • Female
  • Gene Expression / physiology
  • Nerve Regeneration / physiology*
  • Optic Nerve / cytology
  • Optic Nerve / physiology*
  • Rats
  • Rats, Inbred Strains
  • Retinal Ganglion Cells / physiology
  • Retinal Ganglion Cells / ultrastructure
  • Sciatic Nerve / cytology
  • Sciatic Nerve / transplantation*
  • Superior Colliculi / cytology
  • Superior Colliculi / physiology
  • Visual Pathways

Substances

  • Ephrin-A2
  • Ephrin-A5