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

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.

• Authors: A C E Symonds, C E King, C A Bartlett, Y Sauvé, R D Lund, L D Beazley, S A Dunlop, J Rodger
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 25 Issue 3 Pg. 744-52 (Feb 2007) ISSN: 0953-816X [Print] France
• PMID: 17328773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ephrin-A2
• Ephrin-A5

Topics

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