c-fos controls the "private pathway" of light-induced apoptosis of retinal photoreceptors

J Neurosci. 2000 Jan 1;20(1):81-8. doi: 10.1523/JNEUROSCI.20-01-00081.2000.


White light (5 klux for 2 hr) induces apoptosis of rod photoreceptors in wild-type mice (c-fos(+/+)) within 24 hr, whereas rods of c-fos knock-out mice (c-fos(-/-)) are protected (). The range of this protection was tested by analyzing retinas of c-fos(+/+) and c-fos(-/-) mice up to 10 d after exposure to threefold increased light intensities (15 klux for 2 hr). In c-fos(-/-) mice, rods were unaffected, whereas they were destroyed in c-fos(+/+) mice. After light exposure, mitochondrial damage in rods was observed exclusively in c-fos(+/+) mice. Electroretinograms recorded 48 hr after exposure revealed a decrease of all components in c-fos(+/+) mice but indicated no light-induced loss of function in c-fos(-/-) mice. Thus, in c-fos(-/-) mice, light-induced apoptosis is blocked or its threshold is elevated more than threefold. Increased activity of the transcription factor activator protein-1 (AP-1) in retinas of light-exposed c-fos(+/+) mice indicated an acute contribution of AP-1 to apoptosis induction. AP-1 activity increased already during exposure and peaked approximately 6 hr thereafter, coinciding with the appearance of major morphological signs of apoptosis. Activated AP-1 mainly consisted of c-Fos/Jun heterodimers. In c-fos(-/-) mice, AP-1 activity remained unchanged, indicating that no other Jun- or Fos-family member could substitute for c-Fos. Like damaging light, N-methyl-N-nitrosourea (MNU) induced AP-1 containing c-Fos in c-fos(+/+) mice and did not induce AP-1 in c-fos(-/-) mice. In contrast to light, however, MNU induced apoptosis in rods of c-fos(-/-) mice. Thus, c-Fos is essential for a specific premitochondrial "private apoptotic pathway" induced by light but not for the execution of apoptosis induced by other stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • DNA-Binding Proteins / metabolism
  • Dark Adaptation / physiology
  • Disease Models, Animal
  • Electroretinography
  • Female
  • Light / adverse effects
  • Male
  • Methylnitrosourea / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron
  • Mitochondria / physiology
  • Mitochondria / ultrastructure
  • Proto-Oncogene Proteins c-fos / genetics*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / physiopathology*
  • Retinal Rod Photoreceptor Cells / cytology*
  • Retinal Rod Photoreceptor Cells / physiology*
  • Transcription Factor AP-1 / metabolism


  • Alkylating Agents
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-fos
  • Transcription Factor AP-1
  • Methylnitrosourea