Expression of c-Jun protein in degenerating retinal ganglion cells after optic nerve lesion in the rat.
Axonal lesions to the optic nerve (ON) induce c-Jun expression in retinal ganglion cells (RGCs) of the rat in vivo. Detailed investigations using retrograde tracers, and double labeling studies for c-Jun and regeneration-associated factors, such as the growth-associated protein GAP-43, have suggested that this upregulation of c-Jun is part of a cell body response in an abortive attempt of affected RGCs to survive and regenerate an axon. On the other hand, prolonged expression of c-Jun protein has in several paradigms of neurodegeneration been linked to the induction of apoptotic cell death. In the present study, we examined the time course and subcellular localization of c-Jun protein by immunocytochemistry on retinal sections after optic nerve crush and carried out double labeling for c-Jun protein and DNA strand breaks to detect apoptosis on the same sections. Several days after ON lesion, a subpopulation of RGCs was detected in which c-Jun protein was not confined to the nucleus, but also located in the cytoplasm. In addition, RGCs were seen that displayed morphological signs of apoptosis, DNA strand breaks, and c-Jun immunoreactivity at the same time. Therefore, c-Jun expression is not confined to intact or regenerating ganglion cells, but also occurs in cells that are destined to die. Our results suggest that the decision to undergo either fate depends on additional signaling events that modulate the transcriptional actions of c-Jun.
Isenmann
S
S
Max-Planck-Institute for Developmental Biology, University Hospital, Tübingen, Germany.
Bähr
M
M
D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D005260:Female; D005456:Fluorescent Dyes; D005821:Genetic Techniques; D007150:Immunohistochemistry; D007211:Indoles; D009410:Nerve Degeneration / Q000502:physiology*; D009901:Optic Nerve Diseases / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000502:physiology
D005456:Fluorescent Dyes; D007211:Indoles; D016755:Proto-Oncogene Proteins c-jun; C007293:DAPI