Targeting neurodevelopmental miR132-3p promotes neuroprotection and axon regeneration after optic nerve injury in mice

However, it is unknown whether experimental targeting of miR-132 in mature CNS neurons could activate elongation/regeneration of the axons severed by an injury. Here, we characterized miR-132 5p and 3p arm expression during maturation of a prototypical CNS projection neuron, the retinal ganglion cell (RGC), and then tested whether miR-132 arm-specific knockdown (KD) in the RGCs activates elongation/regeneration of axons severed by optic nerve crush (ONC) injury in vivo.

We identified the miR132-3p arm as developmentally-upregulated in the RGCs and found that its KD modestly but significantly promoted RGC axon-regeneration and survival. We also gained insights into the miR132-3p KD-regulated biological processes by transcriptomic profiling of the treated injured RGCs, which showed enrichment of a developmental gene network for formation of axonal projections. Thus, neuronal miR132-3p plays a role in axon regeneration after optic nerve injury, and future studies should investigate the underlying mechanisms.