Retinoic acid receptor β2 promotes functional regeneration of sensory axons in the spinal cord

The embryonic CNS readily undergoes regeneration, unlike the adult CNS, which has limited axonal repair after injury. Here we tested the hypothesis that retinoic acid receptor beta 2 ( RAR beta 2), critical in development for neuronal growth, may enable adult neurons to grow in an inhibitory environment. Overexpression of RAR beta 2 in adult rat dorsal root ganglion cultures increased intracellular levels of cyclic AMP and stimulated neurite outgrowth. Stable RAR beta 2 expression in DRG neurons in vitro and in vivo enabled their axons to regenerate across the inhibitory dorsal root entry zone and project into the gray matter of the spinal cord. The regenerated neurons enhanced second-order neuronal activity in the spinal cord, and RAR beta 2-treated rats showed highly significant improvement in sensorimotor tasks. These findings show that RAR beta 2 induces axonal regeneration programs within injured neurons and may thus offer new therapeutic opportunities for CNS regeneration.