Affiliations: Department of Experimental Ophthalmology, University
Eye Hospital Münster, School of Medicine, Domagkstr. 15, 48149 Münster,
Germany
Note: [] Corresponding author: S. Thanos, Department of Experimental
Ophthalmology, University Eye Hospital Münster, School of Medicine,
Domagkstr. 15, 48149 Münster, Germany. Tel.: +49 251 83 56915 or 56033; Fax:
+49 251 83 56916; E-mail: solon@uni-muenster.de
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.
Keywords: nerve injury, axonal regeneration, nerve grafting, rat retina
