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

Abstract Tumor necrosis factor-alpha (TNF) has been implicated in retinal ganglion cells (RGC) degeneration in glaucoma. Atypical protein kinase C (PKC) ζ is involved in cell protection against various stresses. The aim of this study was to investigate the potential proapoptotic effects of intravitreal injections of TNF with or without PKCζ specific inhibitor on the rat retina. TNF was injected in the vitreous of rat eyes alone or in combination with specific PKCζ inhibitor. PKCζ and NF-κB were studied by immunohistochemistry and western-blotting analysis on retina, and apoptosis quantified by the TUNEL assay. While low basal PKCζ was observed in the control eyes, TNF induced intense expression of PKCζ mostly in bipolar cells processes. PKCζ staining became nuclear when TNF was coinjected with PKCζ inhibitor. TNF alone did not induce apoptosis in the retina. Coinjection of the PKCζ-specific inhibitor and TNF, however, induced apoptosis in the inner nuclear and ganglion cell layers. The PKCζ-specific inhibitor unmasks retinal cells to TNF cytotoxicity showing a link between the proapoptotic effects of TNF and the antiapoptotic PKCζ signaling pathway.