DEPLETION OF FIDGETIN-LIKE 2 FROM CAVERNOUS NERVE INJURY SITES PROMOTES NEURAL REGENERATION AND RECOVERY OF ERECTILE FUNCTION IN A RODENT MODEL OF RADICAL PROSTATECTOMY

The majority of men undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) after the surgery, due to damage to the cavernous nerves (CN). We recently discovered that the enzyme fidgetin-like 2 (FL2), a negative regulator of the microtubule (MT) cytoskeleton, can be targeted in neurons to enhance axon regeneration. Here, we tested the hypothesis that depletion of FL2 from injured CN will promote axon regeneration and recovery of erectile function using a rodent model of RP. Three rat models of CN injury were used: mild (a smooth clamp applied for 2 minutes to the CN), moderate (a serrated clamp applied for 4 minutes to the CN) and severe (CN transection). Immediately after injury, two formulations (nanoparticle or liposomal) for delivery of FL2-siRNA or control-siRNA were applied. Erectile function was assessed at several time points after injury by measuring the intracorporal pressure/blood pressure ratio following electro-stimulation of the CN. To study the effects of FL2 depletion on axon growth and on the microtubule cytoskeleton within the axon shaft in vitro, dissociated adult rodent major pelvic ganglion (MPG) neurons were nucleofected with FL2 or scrambled siRNA, replated 5 days post treatment, then monitored live or fixed and stained for microtubules.