Neurodevelopmental miR-135a-1-3p and miR-135b-3p promote long-distance axon regeneration after injury in the central visual pathway

Here, we characterized the miR-135 family members in the mouse CNS retinal ganglion cell (RGC) and cortical projection neurons development, and tested whether reverting expression towards embryonic levels for the identified developmentally-regulated miR-135 family members may reactivate the intrinsic axon growth capacity following axonal injury in the adult CNS.

We found that, two-out-of-five miR-135 family members, miR-135a-1-3p and miR-135b-3p, were developmentally-downregulated, with further downregulation after axonal injury, in neurons. Importantly, RGC-targeted mimics of miR-135a-1-3p and miR-135b-3p promoted neuroprotection and axon regeneration following optic nerve injury, with axons regrowing through a segment of the central visual pathway when co-treated with axon growth-supporting small fibronectin-based recombinant protein.