Casein kinase-II inhibition promotes retinal ganglion cell survival and axonal regeneration.

Neuron survival is critical for the maintenance of central nervous system physiology upon diseases or injury. We previously demonstrated that the blockage of phosphatidylinositol 3-kinase/Akt and Janus kinase/STAT3 pathways promotes retinal ganglion cell (RGC) survival and axonal regeneration via macrophage activation; yet, the complexity of the inflammatory regulation for neural repair indicates the involvement of additional unresolved signaling pathways. Here we report the effects and underlying mechanism of casein kinase-II (CK2) inhibition on RGC survival and axonal regeneration in rats after optic nerve (ON) injury. Adult rats received intravitreal injection of CK2 inhibitors, TBB (4,5,6,7-Tetrabromo-2-azabenzimidazole) and DMAT (2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole), after ON transection and peripheral nerve (PN) grafting. Intravitreal application of TBB and DAMT effectively suppressed the CK2 phosphorylation activity in the retina, and enhanced RGC survival and axonal regeneration in vivo. Meanwhile, the numbers of infiltrating macrophages were increased. Removal of macrophages by clodronate liposomes significantly abolished the CK2 inhibition-induced RGC survival and axonal regeneration. Clodronate liposomes also weakened the RGC protective effects by TBB and DMAT in vitro. In summary, this study revealed that inhibition of CK2 enhances RGC survival and axonal regeneration via macrophage activation in rats. CK2 could be a therapeutic target for RGC protection after ON injury.