Herpes simplex virus vector-mediated delivery of neurturin rescues erectile dysfunction of cavernous nerve injury.
Neurturin (NTN), a member of glial cell line-derived neurotrophic factor (GDNF) family, is known as an important neurotrophic factor for penis-projecting neurons. We recently demonstrated significant protection from erectile dysfunction (ED) following a replication-defective herpes simplex virus (HSV) vector-mediated GDNF delivery to the injured cavernous nerve. Herein, we applied HSV vector-mediated delivery of NTN to this ED model. Rat cavernous nerve was injured bilaterally using a clamp and dry ice. For HSV-treated groups, 20 microl of vector stock was administered directly to the damaged nerve. Delivery of an HSV vector expressing both green fluorescent protein and lacZ (HSV-LacZ) was used as a control. Intracavernous pressure along with systemic arterial pressure (ICP/AP) was measured 2 and 4 weeks after the nerve injury. Fluorogold (FG) was injected into the penile crus 7 days before being killed to assess neuronal survival. Four weeks after nerve injury, rats treated with HSV-NTN exhibited significantly higher ICP/AP compared with untreated or control vector-treated groups. The HSV-NTN group had more FG-positive major pelvic ganglion neurons than the control group following injury. HSV vector-mediated delivery of NTN could be a viable approach for the improvement of ED following cavernous nerve injury.
Kato
R
R
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Wolfe
D
D
Coyle
C H
CH
Wechuck
J B
JB
Tyagi
P
P
Tsukamoto
T
T
Nelson
J B
JB
Glorioso
J C
JC
Chancellor
M B
MB
Yoshimura
N
N
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D007172:Erectile Dysfunction / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D009416:Nerve Regeneration; D051101:Neurturin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000032:analysis; D010413:Penis / Q000293:injuries* / Q000294:innervation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D051101:Neurturin; D049452:Green Fluorescent Proteins; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase