Abstract
Abstract Introduction Erectile dysfunction (ED) induced by nerve injury including prostatectomy poorly responds to PDE5 inhibitor and requires invasive treatment. Light emitting diodes (LED) in some spectral range, is able to irradiate cells without overheating for its low energy consumption and to enhance mitochondrial metabolism, intracellular energy transfer, and thereby cell proliferation and tissue regeneration in some organs. We, herein, investigated whether and how LED therapy may improve penile erection in mouse cavernous nerve injury (CNI) - induced ED model Objective To identify the optimal LED parameters using molecular, histological, and erectile function analysis in cavernous nerve injury. Methods Eight week old male mice (n=120) were divided into 5 age-matched groups, a sham operation group receiving heat treatment, a CNI group receiving heat treatment, a CNI group receiving red light of LED (wavelength; 660 ±3% nm), a CNI group receiving near infrared light of LED (wavelength; 830 ±2% nm), and a CNI group receiving combination of both LED light. Mice were exposed to LED light for 30 minutes on the ventral side including penis for 5 consecutive days after CNI operation. Molecular study, histopathological analysis of the penis and erectile function test were done 2 weeks following the treatment in each subject. Results CNI group with heat treatment had much lower maximum and total ICP than sham control group. In contrast, three groups with LED light irradiation exhibited considerably improved maximum and total ICP, and the group with both LED treatments had the best erectile performance, reaching 90% of the sham surgery group. Histologically, mice treated with RED, NIR, or LED irradiation had more cavernous pericytes and endothelial cells than CNI mice after sham operation. In addition, all three CNI groups with various LED lengths improved neuroprotection and brain regeneration in CNI mice. All groups treated with LED showed increased expression of βIII-tubulin, neurofilament-1, and nNOS in cavernous tissue and dorsal nerve bundle. Additionally, LED treatment in three groups, particularly the combination group, significantly increased βIII-tubulin, S100, and myelin basic protein levels, indicating axonal integrity or expansion in the dorsal root and major pelvic ganglions. Molecular analysis of downstream signals of neural regeneration or angiogenesis showed that 3 groups with LED treatment increased phosphorylated PI3K, neurotrophic factors like BDNF, NGF, and NT-3, and angiogenic factors like angiopoietin1 and vascular endothelial growth factor in cavernous tissue and llpopolysaccharide-treated PC-12 cells. The TUNEL assay and BrdU staining of these tissue and cells showed lower cell apotosis and proliferation in LED-treated groups. Conclusions The results show that LED therapy with RED, NIR, preferably combination of each wavelength improves penile erection by neural progection or regeneration in cavernous nerve injury induced-ED. This noninvasive therapy may be useful in near future for ED refractory to PDE5 inhibitor. As far as we are aware, this is the first research to demonstrate the advantage of LED therapy, low level in sexual dyfunction field. Disclosure No.
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