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

Brain Res Mol Brain Res. 1999 Jun 8;69(2):232-41. doi: 10.1016/s0169-328x(99)00113-8.

Abstract

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 hybridization. Optic nerve injury led exclusively to the upregulation of c-jun, with cellular label indicative for c-jun mRNA in the retinal ganglion cell layer after two days, three days and one week post-injury. This expression pattern was in accordance with the appearance of c-Jun immunoreactivity in retinal flat mounts. Injection of an antisense but not a missense oligonucleotide against c-jun after partial crush resulted in a reduced number of connected retinal ganglion cells (RGCs) as shown by retrograde labeling. Prelabeling of RGCs with fluorogold before optic nerve section and subsequent antisense targeting against c-jun, however, led to a slightly higher number of surviving but axotomized RGCs. C-Jun antibody staining of retinal whole mounts pre- or postlabeled after crush by intracollicular administration of fluorogold showed strong c-Jun immunoreactivity in connected RGCs and also in a population of disconnected RGCs. Double labeling with an antibody directed 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 together these data indicate that both RGCs in continuity and those in discontinuity with the superior colliculus respond both equally to the noxious stimulus with c-Jun expression. Moreover, the co-expression of c-Jun with high levels of ATF-2 appears to be essential for either the continuity or survival of RGCs which remain connected with their target. In disconnected RGCs, however, low levels of ATF-2 and the co-expression of c-Jun may be related to cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 2
  • Animals
  • Axons / metabolism*
  • Axotomy
  • Cell Survival / physiology
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Gene Expression Regulation / physiology*
  • In Situ Hybridization
  • Nerve Crush
  • Nerve Tissue Proteins / genetics*
  • Neural Pathways / physiology
  • Oligonucleotides, Antisense
  • Optic Nerve / metabolism
  • Optic Nerve / ultrastructure
  • Optic Nerve Injuries*
  • Proto-Oncogene Proteins c-jun / genetics
  • Rats
  • Rats, Inbred Strains
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism*
  • Transcription Factors / genetics

Substances

  • Activating Transcription Factor 2
  • Atf2 protein, rat
  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-jun
  • Transcription Factors