Changes in the expression of transcription factors ATF-2 and Fra-2 after axotomy and during regeneration in rat retinal ganglion cells

Abstract

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 immunohistochemistry combined with retrograde labeling to examine the expression of two additional bZip transcription factors (ATF-2 and Fra-2) in identified adult rat RGCs under favorable and unfavorable conditions for axonal regrowth. For unfavorable regrowth conditions, ganglion cell axons within the optic nerve were cut close to the eye. For favorable conditions, the optic nerve was replaced with an autologous peripheral nerve graft to allow axonal regrowth. At regular intervals after axotomy alone or in conjunction with graft placement, the expression of these transcription factors was examined in retinal wholemounts using protein-specific antibodies. The strong cytoplasmic expression of Fra-2 seen in unaxotomized RGCs was reduced beginning 24 h after axotomy. Similarly, the strong nuclear expression of ATF-2 seen prior to axotomy was also reduced after axotomy. These reductions persisted in surviving ganglion cells throughout the 3 week study period. One to 6 months after axotomy and peripheral nerve graft placement, identified RGCs with regrown axons showed strong ATF-2 and Fra-2 expression, suggesting a return to basal conditions. These findings support roles for ATF-2 and Fra-2 in the survival and regeneration processes of these central nervous system neurons after axotomy.