CHANGES IN THE EXPRESSION OF TRANSCRIPTION FACTORS ATF-2 AND FRA-2 AFTER AXOTOMY AND DURING REGENERATION IN RAT RETINAL GANGLION-CELLS

The expression of one member of the bZip superfamily of transcription factors, c-Jun, is known to be induced by axotomy in retinal ganglion cells (RGCs) and is associated with axonal regrowth. This study used i mmunohistochemistry combined with retrograde labeling to examine the e xpression of two additional bZip transcription factors (ATF-2 and Fra- 2) in identified adult rat RGCs under favorable and unfavorable condit ions for axonal regrowth. For unfavorable regrowth conditions, ganglio n cell axons within the optic nerve were cut close to the eye. For fav orable conditions, the optic nerve was replaced with an autologous per ipheral nerve graft to allow axonal regrowth. At regular intervals aft er axotomy alone or in conjunction with graft placement, the expressio n of these transcription factors was examined in retinal wholemounts u sing protein-specific antibodies. The strong cytoplasmic expression of Fra-2 seen in unaxotomized RGCs was reduced beginning 24 h after axot omy. Similarly, the strong nuclear expression of ATF-2 seen prior to a xotomy was also reduced after axotomy. These reductions persisted in s urviving ganglion cells throughout the 3 week study period. One to 6 m onths after axotomy and peripheral nerve graft placement, identified R GCs with regrown axons showed strong ATF-2 and Fra-2 expression, sugge sting a return to basal conditions. These findings support roles for A TF-2 and Fra-2 in the survival and regeneration processes of these cen tral nervous system neurons after axotomy.