Herpes simplex virus vector-mediated delivery of neurturin rescues erectile dysfunction of cavernous nerve injury

Gene Ther. 2009 Jan;16(1):26-33. doi: 10.1038/gt.2008.132. Epub 2008 Jul 31.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Erectile Dysfunction / etiology
  • Erectile Dysfunction / metabolism
  • Erectile Dysfunction / therapy*
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins / genetics
  • Immunohistochemistry
  • Male
  • Models, Animal
  • Nerve Regeneration
  • Neurturin / analysis
  • Neurturin / genetics*
  • Neurturin / metabolism
  • Nitric Oxide Synthase Type I / analysis
  • Penis / injuries*
  • Penis / innervation
  • Rats
  • Rats, Sprague-Dawley
  • Simplexvirus / genetics*
  • Transduction, Genetic / methods
  • Tyrosine 3-Monooxygenase / analysis

Substances

  • Biomarkers
  • Neurturin
  • Green Fluorescent Proteins
  • Nitric Oxide Synthase Type I
  • Tyrosine 3-Monooxygenase