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 prot eins) and cAMP-responsive element binding protein (CREBP) were examine d by immunohistochemistry under three different paradigms. Normal rats which were not axotomized were compared with axotomized animals, wher e retinal ganglion cells (RGCs) were axotomized by intraorbital optic nerve cut and retrogradely labeled with fluorogold (FG). Under these c ircumstances, RGCs show only transient sprouting, followed by continuo us retrograde RGC degeneration. In the third group, after the optic ne rve 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 th e 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 starte d to decline 8 days after axotomy. Only a few JUN-Ir-positive RGCs wer e found after 2 weeks. In transplanted animals, however, the numbers o f JUN-Ir-positive RGCs were significantly higher 2 and 3 weeks after t ransplantation compared to animals that exclusively received axotomy. Furthermore, in grafted rats, about 70% of the regenerating RGCs expre ssed JUN-Ir 2 weeks after grafting as compared to only 38% JUN-positiv e RGCs among the surviving but not regenerating RGCs. In normal animal s CREBP-Ir was constitutively expressed in nearly all cells of the ret inal ganglion cell layer. The decline in number of CREBP-Ir-positive c ells paralleled the axotomy-induced RGC death. FOS-Ir-positive cells w ere not found in the ganglion cell layer at any time. These results de monstrate a selective and transient JUN expression of RGCs after axoto my which is sustained during axonal regeneration. This suggests that s ciatic nerve grafts are able to regulate the expression of JUN protein s in axotomized RGCs of adult rats. (C) 1994 John Wiley & Sons, Inc.