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Introduction Radical prostatectomy (RP) often causes erectile dysfunction (ED) because of cavernous nerve damage during surgery. This damage results in a decrease of nitric oxide (NO) in the penile corpus cavernosum. Therefore, NO supplementation is considered to be effective for post RP ED. However, NO has systemic side effects such as headache and hypotension. Recently, a red-light-controlled NO donor “NORD-1”, developed by our group, enables spatially and temporally controlled NO release by light irradiation. Our previous study reported that NORD-1 combined with red-light irradiation is effective for neurogenic ED model rats with bilateral cavernous nerve injury (BCNI). However, the side effects of the treatment have not yet been discussed. Objective The study aimed to investigate the potency of side effects associated with the combination of NORD-1 and red-light irradiation, using a ED rat model with BCNI. Methods In this study, eight-week-old male Wistar-ST rats were used. The rats were divided into four groups: Sham+SiR650 (control compound), Sham+NORD-1, BCNI+SiR650, and BCNI+NORD-1 (n=6). The sham or BCNI surgery was performed under anesthesia in each group. BCNI surgery was performed by crushing the cavernous nerves bilaterally. Four weeks post-surgery, erectile function before and after the injection of each reagent into the penile corpus cavernosum was evaluated based on the changes in intracavernous pressure (ICP) under electrostimulation of the cavernous nerve. After the administration of each reagent, the changes in ICP with and without light irradiation were also evaluated. ICP during electrostimulation was totally measured three times; once without reagent and light, once with reagent and without light and once with reagent and light. The variations in systemic arterial pressure during electrostimulation were also analyzed. After the experiment, penile samples were collected to observe NORD-1 localization using a fluorescence microscope. In addition, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis in the corpus cavernousm. Results Before administering each reagent without light irradiation, the ICP/mean arterial pressure (MAP) ratios under stimulation in the BCNI+SiR650 and BCNI+NORD-1 groups were significantly lower than those in the Sham+SiR650 (P < 0.01) and Sham+NORD-1 (P < 0.05) groups. After administering each reagent without light irradiation, the ICP/MAP ratios in the BCNI+SiR650 and BCNI+NORD-1 groups remained significantly lower than those in the Sham+SiR650 and Sham+NORD-1 group (P < 0.05 and P < 0.01, respectively). After administering each reagent with light irradiation, the ICP/MAP ratios in the Sham+NORD-1 and BCNI+NORD-1 groups were significantly higher than those in the Sham+SiR650 (P < 0.01) and BCNI+NORD-1 (P < 0.01) groups, respectively. The changes of MAP during electrostimulation were not different under three different conditions in all four groups. Fluorescence of NORD-1 was detected only in corpus cavernousum which means it was not detected in urethra and dorsal vein of penis. Apoptosis was not detected in corpus cavernousum in all four groups. Conclusions The combination of NORD-1 and light irradiation is effective for neurogenic ED in rats with cavernous nerve injury. The treatment may not cause hypotension and tissue damage. Disclosure No

Introduction Radical prostatectomy often causes erectile dysfunction (ED). This is considered to be due to surgery-induced nerve damage. Impairments in neurotransmission result in the release of nitric oxide (NO) in penile corpus cavernosum insufficiency. Therefore, phosphodiesterase-5 inhibitors are not necessarily effective for this type of ED. NO supplementation may be effective for this type of ED. However, NO acts on the whole body and thus may cause adverse effects. Recently, we have developed a light-controlled NO donor that enables spatially and temporally controlled NO release by light irradiation. Whether this type of NO donor is useful for neurogenic ED remains unknown. Objective We investigated whether this light-controlled NO donor “NORD-1” and light irradiation were effective for managing neurogenic ED in rats with bilateral cavernous nerve injury (BCNI). Methods We used eight-week-old male Wistar-ST rats. The rats were divided into four groups: Sham+SiR650 (control compound) (n=5), Sham+NORD-1 (n=5), BCNI+SiR650 (n=6), and BCNI+NORD-1 (n=6). Initially, sham or BCNI surgery was performed under anesthesia in each group. BCNI surgery was performed by crushing the bilateral cavernous nerves. Four weeks post-surgery, erectile function before and after the injection of each compound into the penile corpus cavernosum was evaluated based on the change in intracavernous pressure (ICP) under electrical stimulation of the cavernous nerve. The changes in ICP with and without light irradiation were also evaluated after the administration of each compound. Results Before administering each treatment without light irradiation, the ICP/mean arterial pressure (MAP) ratio under stimulation in the BCNI+SiR650 and BCNI+NORD-1 groups were lower than those in the Sham+SiR650 (P Conclusions The combination of NORD-1 and light irradiation may be useful for treating neurogenic ED, although its toxicity must be evaluated. Disclosure Work supported by industry: no.