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Role of GSK 3 activity in optic nerve regeneration
Author(s) -
Fischer D.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.03523
Subject(s) - regeneration (biology) , optic nerve , axon , neuroprotection , neuroscience , context (archaeology) , conditional gene knockout , microbiology and biotechnology , inhibitory postsynaptic potential , retina , biology , phenotype , biochemistry , paleontology , gene
Summary Retinal ganglion cells ( RGC s) do not normally regenerate axons upon optic nerve injury. However, inflammatory stimulation ( IS ) significantly enables axon growth in the injured optic nerve. Here, we demonstrate that optic nerve crush strongly induces inhibitory phosphorylation of GSK 3 α and GSK 3 β in RGC s. To investigate the role of GSK 3 in this context we tested IS induced regeneration and neuroprotection in conditional GSK 3 α and GSK 3 β knockout mice ( GSK 3 α ‐/‐ , GSK 3 β ‐/‐ ) as well as GSK 3 α S/A and GSK 3 β S/A mice expressing resistant GSK 3 isoforms to this inhibitory phosphorylation. In contrast to GSK 3 α ‐/‐ , GSK 3 β ‐/‐ markedly potentiated IS induced optic nerve regeneration. On the contrary, IS mediated regeneration was significantly reduced in GSK 3 S/A mice. These findings suggest that active GSK 3 intrinsically limits the outcome of CNS axon regeneration. Thus, treatments activating the intrinsic growth state combined with GSK 3 β inhibition might be suitable to further improve the regenerative outcome after CNS injury.