Contribution of caspase-8 to apoptosis of axotomized rat retinal ganglion cells in vivo

Neurobiol Dis. 2003 Jul;13(2):124-35. doi: 10.1016/s0969-9961(03)00032-9.


We have investigated the role of caspase-8 and its mode of activation during apoptosis of adult rat retinal ganglion cells (RGCs) in vivo. Retinal pro-caspase-8 expression was almost completely restricted to RGCs. Although caspase-8 is known to be involved in death-receptor-dependent apoptosis, measurable caspase-8 activity or even RGC death could be induced by neither tumor necrosis factor-alpha nor Fas ligand injections into unlesioned eyes. However, substantial caspase-8 activation could be detected after optic nerve transection as shown by a fluorogenic activity assay and Western blot analysis. Intravitreal injection of caspase-8 inhibitors significantly attenuated degeneration of RGCs and reduced the number of RGCs showing caspase-3 activation. A late peak of caspase-8 activity and additive protective effects of caspase-8 and -9 inhibition on axotomized RGCs place caspase-8 in our model rather late in the apoptosis cascade, possibly after the onset of mitochondrial dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Axotomy*
  • Blotting, Western
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Cell Count
  • Female
  • Immunohistochemistry
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells / enzymology*
  • Time Factors


  • Casp3 protein, rat
  • Casp8 protein, rat
  • Casp9 protein, rat
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases