Session: MP60: Bladder and Urethra: Anatomy, Physiology and Pharmacology
MP60-13: Viral transduction efficacy of peripheral neurons innervating the external urethral sphincter by local injection of adeno-associated virus vectors
Introduction: Incomplete functional recovery of the lower urinary tract, including the external urethral sphincter (EUS), frequently occurs in spinal cord injury patients. Electrical neuromodulation of the lower urinary tract remains an attractive therapeutic target, but it has yet to be fully deployed clinically. The wide distribution of sensory and motor axons in the pudendal nerve innervating targets in the lower urinary tract but also other targets in other pelvic structures significantly limits the development of electrical neuromodulation strategies. We can address this limitation by using optogenetic techniques to modulate the lower urinary tract using light stimulation. First, we need to determine the viral vectors' efficiency and potential promoters to transduce the specific neuronal populations through local injection into regions of the lower urinary tract. In this study, we investigated the transduction efficiency of adeno-associated virus serotypes in the peripheral regions by local injection into the external urethral sphincter. Methods: We injected different AAV vector serotypes along with a neural tracer into the external sphincter of rats. After five weeks, we evaluated the viral transduction efficiency of these AAV serotypes. Results: We observed variable transduction of multiple peripheral neuron populations and showed different efficacies of neuronal transduction by these viruses compared with labeling with a neural tracer. We also found that this level of expression by local injection is also relevant for optogenetic-mediated modulation of the EUS function. Conclusions: Our preliminary results indicate that by using adeno-associated viruses, it is possible to transduce the neurons controlling the EUS by local injection. We think these studies will potentially help improve the viral targeting of neurons controlling lower urinary tract function. SOURCE OF Funding: This research was supported by the NIH NIBIB Trailblazer award (R21 EB031249) and in part by the Urology Care Foundation Research Scholar Award Program and Indian American Urological Association Sakti Das, MD Award
