Regeneration of ganglion cell axons into a peripheral nerve graft alters retinal expression of glial markers and decreases vulnerability to re-axotomy.

Abstract

PURPOSE:

To compare the effect of cutting the optic nerve versus replacing the cut optic nerve with a peripheral nerve (PN) graft on retinal glial markers, and to determine whether the PN graft can stabilize regenerating retinal ganglion cells (RGCs), thus preventing their death following re-axotomy.

METHODS:

Retinas harvested after ganglion cell regeneration into a sciatic nerve graft were compared to untreated control retinas and retinas obtained following optic nerve axotomy. Glial-specific proteins such as glial fibrillary acidic protein (GFAP), Bcl-2 and complement-3 receptor (Ox-42) were examined using immunohistochemistry. Ganglion cells that survived the second axotomy were quantified on retinal flat mounts by retrograde labeling from the graft.

RESULTS:

GFAP expression in astrocytes and Muller cells was elevated in axotomized retinas when compared to controls, and an additional up-regulation in Muller cells was found in retinas following ganglion cell regeneration. Increased GFAP expression in retinas containing regenerated neurons was accompanied by increased Bcl-2 expression with latter being confined to Muller cells. Moreover, re-axotomy of the regenerated axons within the graft did not result in significant retrograde degeneration of RGCs within 28 days.

CONCLUSIONS:

The data suggest that the graft stabilizes the regenerating RGCs to an extent reminiscent of peripheral neurons, a process that may involve the interaction between neuronal and glial elements.

• Authors: Erik Schuetz, Karin Rose, Solon Thanos
• Journal: Restorative neurology and neuroscience (Restor Neurol Neurosci) Vol. 21 Issue 1-2 Pg. 11-8 ( 2003) ISSN: 0922-6028 [Print] Netherlands
• PMID: 12808198 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Glial Fibrillary Acidic Protein
• hoechst 32258

Topics

• Animals
• Axons (physiology)
• Axotomy (methods)
• Benzimidazoles (pharmacokinetics)
• Cell Count
• Cell Survival
• Female
• Gene Expression Regulation
• Glial Fibrillary Acidic Protein (genetics, metabolism)
• Immunohistochemistry
• Male
• Nerve Degeneration (metabolism, physiopathology)
• Nerve Regeneration (physiology)
• Optic Nerve (anatomy & histology)
• Rats
• Rats, Sprague-Dawley
• Retina (cytology, metabolism)
• Retinal Ganglion Cells (metabolism, physiology)
• Sciatic Nerve (transplantation)
• Time Factors