Co-expression of c-Jun and ATF-2 characterizes the surviving retinal ganglion cells which maintain axonal connections after partial optic nerve injury

The expression of c-fos. c-jun, jun-b, jun-d, srf and pc4 mRNA was examined after partial optic nerve crush in the adult rat retina by in situ hybridi zation. Optic nerve injury led exclusively to the upregulation of c-jun, wi th cellular label indicative for c-jun mRNA in the retinal ganglion cell la yer after two days, three days and one week post-injury. This expression pa ttern was in accordance with the appearance of c-Jun immunoreactivity in re tinal flat mounts. Injection of an antisense but not a missense oligonucleo tide against c-jun after partial crush resulted in a reduced number of conn ected retinal ganglion cells (RGCs) as shown by retrograde labeling. Prelab eling of RGCs with fluorogold before optic nerve section and subsequent ant isense targeting against c-jun, however, led to a slightly higher number of surviving but axotomized RGCs. C-Jun antibody staining of retinal whole mo unts pre- or postlabeled after crush by intracollicular administration of f luorogold showed strong c-Jun immunoreactivity in connected RGCs and also i n a population of disconnected RGCs, Double labeling with an antibody direc ted against the transcription factor ATF-2 revealed strong co-expression of c-Jun and ATF-2 in connected RGCs but not in axotomized cells. Taken toget her these data indicate that both RGCs in continuity and those in discontin uity with the superior colliculus respond both equally to the noxious stimu lus with c-Jun expression Moreover, the co-expression of c-Jun with high le vels of ATF-2 appears to be essential for either the continuity or survival of RGCs which remain connected with their target. In disconnected RGCs. ho wever, low levels of ATF-2 and the co-expression of c-Jun may be related to cell death. (C) 1999 Elsevier Science B.V. All rights reserved.