Survival of axotomized retinal ganglion cells in peripheral nerve-grafted ferrets.

PURPOSE: Peripheral nerve (PN) grafting to the optic nerve stump stimulates not only axonal regeneration of the axotomized retinal ganglion cells (RGCs) into the grafted PN but also their survival. The purpose of the present study was to determine the number, distribution, and soma diameter of only surviving RGCs without regenerated axons and surviving RGCs with regenerated axons in PN-grafted mammals. METHODS: A segment of PN was grafted to the optic nerve stump of adult ferrets. Two months after the PN grafting, surviving RGCs with regenerated axons were retrogradely labeled with granular blue (GB) and stained with RGC-specific antibody C38. Surviving RGCs without regenerated axons were identified as C38-positive cells without GB labeling. RESULTS: Twenty-one percent of RGCs survived axotomy after PN grafting in the area centralis (AC), whereas 47% survived in the peripheral retina. Twenty-six percent of surviving RGCs in the AC exhibited axonal regeneration, which was higher than that in the peripheral retina. Soma diameter histograms revealed that RGCs with regenerated axons showing both GB and C38 positivity were in the large soma diameter ranges. In contrast, the soma diameter distribution of surviving RGCs that did not have regenerated axons showed a peak in the smaller soma diameter ranges. CONCLUSIONS: The present data suggest that PN grafting promotes survival of axotomized RGCs more effectively in the peripheral retina than in the AC. Among surviving RGCs, the larger cells exhibited axonal regeneration into the grafted PN, whereas the axons of smaller cells did not to regenerate in either the AC or the peripheral retina.

Localization of FGFR-1 in axotomized and peripheral nerve transplanted ferret retina.

Retinal ganglion cells (RGCs) survive axotomy and regenerate their axons into the peripheral nerve graft in adult mammals. To understand the potential role of fibroblast growth factors (FGFs) in survival and regeneration of axotomized RGCs, we examined FGF receptor 1 (FGFR-1) localization in normal and PN grafted ferret retinas by immunohistochemistry in combination with retrograde labeling. Prominent expression of FGFR-1 was observed in outer plexiform layer and ganglion cell layer of normal ferret retina. In the ganglion cell layer, FGFR-1 immunoreactivity was detected in about 30% of RGCs, predominantly in large cells. In the PN grafted ferret retina, 90% of RGCs with regenerated axons expressed FGFR-1. Our findings suggest that FGFs may play an important role in the survival and axonal regeneration of RGCs of adult mammals.