Regulation of immediate-early gene expression in rat retinal ganglion cells after axotomy and during regeneration through a peripheral nerve graft.
To determine mechanisms of structural plasticity in adult CNS neurons, we investigated the expression of immediate early genes (IEGs) in the rat retina. Gene products of different IEG families (JUN and FOS proteins) and cAMP-responsive element binding protein (CREBP) were examined by immunohistochemistry under three different paradigms. Normal rats which were not axotomized were compared with axotomized animals, were retinal ganglion cells (RGCs) were axotomized by intraorbital optic nerve cut and retrogradely labeled with fluorogold (FG). Under these circumstances, RGCs show only transient sprouting, followed by continuous retrograde RGC degeneration. In the third group, after the optic nerve lesion, adult rats additionally received a sciatic nerve graft to the transected optic nerve stump. This allows some RGCs to regenerate an axon into the grafted nerve. In both groups, the time course of RGC survival and JUN, CREB, and FOS protein expression was monitored. In normal animals, JUN-Immunoreactivity (JUN-Ir) was not detectable in the retinal ganglion cell layer. JUN-Ir was induced in about 70% of all FG-positive RGCs 5 days after axotomy. The expression of JUN-Ir stated to decline 8 days after axotomy. Only a few JUN-Ir-positive RGCs were found after 2 weeks. In transplanted animals, however, the numbers of JUN-Ir-positive RGCs were significantly higher 2 and 3 weeks after transplantation compared to animals that exclusively received axotomy. Furthermore, in grafted rats, about 70% of the regenerating RGCs expressed JUN-Ir 2 weeks after grafting as compared to only 38% JUN-positive RGCs among the surviving but not regenerating RGCs. In normal animals CREBP-Ir was constitutively expressed in nearly all cells of the retinal ganglion cell layer. The decline in number of CREBP-Ir-positive cells paralleled the axotomy-induced RGC death. FOS-Ir-positive cells were not found in the ganglion cell layer at any time. These results demonstrate a selective and transient JUN expression of RGCs after axotomy which is sustained during axonal regeneration. This suggests that sciatic nerve grafts are able to regulate the expression of JUN proteins in axotomized RGCs of adult rats.
Hüll
M
M
Neurologische Universitätsklinik, Tübingen, Federal Republic of Germany.
Bähr
M
M
D051698:Activating Transcription Factor 2; D000818:Animals; D001369:Axons / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology / Q000378:metabolism; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000502:physiology*; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis / Q000276:immunology; D016761:Oncogene Proteins v-fos / Q000096:biosynthesis / Q000276:immunology; D009900:Optic Nerve / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology* / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000502:physiology / Q000637:transplantation; D013266:Stilbamidines; D014157:Transcription Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D005456:Fluorescent Dyes; D016759:Oncogene Protein p65(gag-jun); D016761:Oncogene Proteins v-fos; D013266:Stilbamidines; D014157:Transcription Factors