Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal ganglion cells by optic nerve transection

Invest Ophthalmol Vis Sci. 2002 May;43(5):1631-5.

Abstract

Purpose: To examine the involvement of c-Jun and c-Jun N-terminal phosphorylation (JNP) in apoptosis of retinal ganglion cells (RGCs) after the optic nerve (ON) transection.

Methods: The expression and phosphorylation of c-Jun protein and apoptosis in RGCs were examined after ON transection in wild-type mice and mice in which both phosphoacceptor serines of Jun have mutated to alanines (c-Jun[AA] mice). The fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was applied to the superior colliculi (SC), and the right ON was severed after 7 days. After two more weeks, the average number of RGCs per field was calculated.

Results: JNP and TUNEL-labeled apoptotic nuclei were detected in the ganglion cell layer (GCL) of the retina of the wild-type mice in response to ON transection. The numbers of TUNEL-positive nuclei in the c-Jun(AA) mice was reduced in comparison to those in wild-type mice. Retrograde labeling showed that the number of the RGCs in the retinas on the injured side of the c-Jun(AA) mice was significantly higher than in wild-type mice 14 days after the lesion.

Conclusions: These results suggest that there is a partial but significant contribution of JNP to the induction of apoptosis in RGCs by ON transection.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Carbocyanines
  • Cell Count
  • Cell Nucleus
  • Cell Survival
  • In Situ Nick-End Labeling
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mice, Mutant Strains
  • Mitogen-Activated Protein Kinases / metabolism*
  • Optic Nerve / metabolism
  • Optic Nerve Injuries / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Retinal Ganglion Cells / metabolism*

Substances

  • 3,3'-dihexadecylindocarbocyanine
  • Carbocyanines
  • Proto-Oncogene Proteins c-jun
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases