Expression of JUN, KROX, and CREB transcription factors in goldfish and rat retinal ganglion cells following optic nerve lesion is related to axonal sprouting

Abstract

Goldfish and rat optic nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and upto 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After optic nerve cut in goldfish, a JUN-like immunoreactivity (JUN-IR) appeared in a small number of RGCs of central retina after 24 h, reached a maximum within 5 days, declined after 30 days, and was on a half-maximal level after 50 days. Between 100 and 200 days, JUN-IR was only visible in a few RGCs and was completely absent after 350 days. Specific antibodies against c-JUN, JUN B, and JUN D gave no distinct immunoreactive signal. Thus, we could not determine which member of the JUN family contributed to the JUN-IR. The expression of CREB declined after 5 days. The number of CREB-labeled RGCs was reduced (not significant) and the intensity of labeling faded out. After 50 days, CREB-IR had returned to basal level. c-FOS, FOS B, and KROX-24 could not be detected in goldfish RGCs following optic nerve cut. After optic nerve crush in the rat, c-JUN, JUN D, and KROX-24 appeared in a substantial number of RGCs after 24 h, had a maximal expression after 5 days, and strongly declined after 8 days. c-JUN and KROX-24 were completely absent after 22 days whereas JUN D was still present in a few rat RGCs. The number of CREB-labeled RGCs decreased after 5 days and had declined by 50% after 22 days. Expression of JUN B, c-FOS, FOS B could not be detected in rat RGCs after optic nerve crush. Our data demonstrate that the decrease of CREB and the increase of JUN and KROX-24 transcription factors precedes and parallels both the alteration of de novo protein synthesis and the axonal sprouting, which are long lasting in goldfish and transient in rat.