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Protein kinase C-zeta mediates retinal degeneration in response to TNF

Hong Liang1, Christophe Baudouin, Francine Behar-Cohen

  • 1INSERM, U598, Physiopathology of ocular diseases: therapeutic innovations, Department of Ophthalmology, Quinze-Vingts National Ophthalmology Hospital, AP-HP, Paris Ouest School of Medicine, Paris, France.

Journal of Neuroimmunology
|January 9, 2007
PubMed

Insights

Tumor necrosis factor-alpha (TNF) did not cause retinal cell death alone. However, inhibiting protein kinase C zeta (PKCzeta) with TNF induced apoptosis in retinal ganglion cells, revealing a protective role for PKCzeta.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Cell Biology

Background:

  • Glaucoma is associated with retinal ganglion cell (RGC) degeneration, potentially mediated by tumor necrosis factor-alpha (TNF).
  • Atypical protein kinase C zeta (PKCzeta) plays a role in cellular protection against stress.

Purpose of the Study:

  • To investigate the proapoptotic effects of intravitreal TNF injections, with or without a specific PKCzeta inhibitor, on rat retinas.
  • To elucidate the interplay between TNF and PKCzeta signaling in retinal cell survival and apoptosis.

Main Methods:

  • Intravitreal injections of TNF and/or a PKCzeta-specific inhibitor in rat eyes.
  • Immunohistochemistry and Western blotting to analyze PKCzeta and NF-kappaB expression.
  • TUNEL assay to quantify apoptosis in retinal tissues.

Main Results:

  • TNF alone did not induce retinal apoptosis but increased PKCzeta expression in bipolar cells.
  • Coinjection of TNF with the PKCzeta inhibitor led to apoptosis in the inner nuclear and ganglion cell layers.
  • PKCzeta inhibition unmasked retinal cells to TNF-induced cytotoxicity.

Conclusions:

  • The study demonstrates a link between TNF's proapoptotic effects and the antiapoptotic PKCzeta signaling pathway.
  • PKCzeta acts as a protective factor against TNF-induced retinal cell death.
  • Targeting PKCzeta may influence therapeutic strategies for glaucoma and related optic neuropathies.

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