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Ling Ping Cen; Casein Kinase 2 Pathway Inhibition Promotes Retinal Ganglion Cell Survival and axon regeneration via Macrophage Activation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4408.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the roles of casein kinase 2 (CK2) pathway in RGC survival and axon regeneration after optic nerve (ON) injury.
Adult rats received ON transection and a peripheral nerve (PN) graft onto proximal end of the ON stump to provide a favourable environment for axon regrowth. Intravitreal injections of CK2 inhibitor TBB or DMAT were performed at 3, 9, and 15 days after ON surgery. Animals survived for 3 weeks. Three days before animal sacrifice, FluoroGold was injected into distal end of the PN graft to retrogradely label axon-regenerating RGCs. After counting FG-labled RGCs, retinas were double-immunostained with TUJ1 antibody to identify viable RGCs and ED1 antibody to reveal macrophages. CK2 activity assay was applied to the effectiveness in blocking the signal transduction of CK2 pathway of the 2 inhibitors.
TBB or DMAT led to macrophage activation in the eye and enhanced RGC survival and axon regeneration. Removal of macrophages in the eyes using clodronate liposomes completely abolished CK2 inhibitors-induced RGC survival and substantially decreased axon regeneration. CK2 assay confirmed the effectiveness of TBB or DAMT in inhibiting CK2 signal transduction.
Our data demonstrate that whereas CK2 pathway itself does not participate in the process leading to RGC death after ON injury, inhibition of this pathway activates macrophages in the eyes to facilitate RGC survival and axon regeneration.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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