(008) SONIC HEDGEHOG TREATMENT SUPPRESSES LONG TERM PENILE REMODELING AFTER CAVERNOUS NERVE INJURY

Abstract Introduction Cavernous nerve (CN) injury, which occurs in prostatectomy and diabetic patients, initiates penile remodeling, including smooth muscle apoptosis and increasing collagen in the corpora cavernosa, which are underlying causes of erectile dysfunction (ED); Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle and SHH treatment suppresses corpora cavernosa remodeling that occurs with CN injury. Objective We examined if SHH treatment by peptide amphiphile (PA) in the first week after CN injury is sufficient to prevent long term penis remodeling and examined if apoptosis inhibitors also suppress penile remodeling. Methods Bilateral CN crush was performed on adult (P115-120) Sprague Dawley rats that underwent one of three treatments using novel extended-release nanofiber PA hydrogels for delivery: 1.) SHH protein (n = 10), 2.) Mouse serum albumin (MSA) protein (control, n = 7), or 3.) Caspase 3 inhibitor (AC-DEVD-CHO, n = 10). Rats were sacrificed after 18-24 days. Additional rats underwent CN injury (n = 6), or CN injury and SHH PA treatment for 2 and 4 days (n = 8), sham controls (n = 3), and non-surgery controls (n = 3). Trichrome stain, hydroxyproline assay, and western analysis for -actin (smooth muscle) and GAPDH, were performed to examine smooth muscle retention and collagen abundance. Results Smooth muscle decreased with CN injury. Corpora cavernosa showed increased smooth muscle at 2, 4 and 18-24 days after CN injury with SHH PA treatment in comparison to MSA treated CN injured controls. Caspase 3 inhibited penis showed little smooth muscle preservation. Collagen was decreased 23% with SHH PA treatment (p < 0.001), at 18-24 days after CN injury. Collagen was unchanged with caspase 3 inhibitor treatment (p = 1.000). Conclusions SHH treatment by PA in the first week after CN injury is sufficient to suppress penile remodeling, and to preserve penile smooth muscle over time, which is critical to prevent ED. It is important to know that treatments given at the time of CN injury have a sustained effect on preserving penile architecture, and thus erectile function, making them valuable for clinical translation. Disclosure No.