Abstract
After rhizotomy, axonal regeneration in the dorsal root is arrested in the transition zone between the peripheral and central nervous system. The damaged sensory axons have been shown to grow across this inhibitory dorsal root entry zone (DREZ) with the provision of neurotrophic factors1. In this study we present a novel approach to stimulating axonal growth across this barrier via the use of an equine infectious anaemia virus (EIAV)-based lentiviral vector expressing a novel regenerative molecule. Retinoic acid receptor β2 (RARβ2) is a transcription factor activated by retinoic acid, a biologically active metabolite of Vitamin A, and has been shown to induce neurite outgrowth in adult spinal cord explants2. An EIAV-based lentiviral vector expressing RARβ2 was delivered to sensory neurones via injection into dorsal spinal cord. In control animals that received an EIAV vector expressing β-galactosidase (LacZ), dorsal rhizotomy resulted in the loss of peripheral sensory axons innervating the spinal cord corresponding to the injured roots. In contrast, injured primary sensory afferents were found to regenerate across the DREZ in RARβ2 animals. Furthermore RARβ2-treated animals exhibited improvement in performance in behavioural tasks assessing for sensory and motor functions. These results suggest that lentiviral-mediated delivery of RARβ2 promoted the regeneration of injured sensory axons into the inhibitory DREZ after rhizotomy and promoted functional recovery. Hence this novel approach shows potential for therapeutic applications in the treatment of dorsal root avulsion injuries.
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