Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity.
Gentamicin administration often results in cochlear and/or vestibular hair cell loss and hearing and balance impairment. It has been demonstrated that adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) can protect cochlear hair cells against ototoxic injury. In this study, we evaluated the protective effects of adenovirus-mediated overexpression of GDNF against gentamicin ototoxicity. An adenovirus vector expressing the human GDNF gene (Ad.GDNF) was administered into the scala vestibuli as a rescue agent at the same time as gentamicin, or as a protective agent, 7 days before gentamicin administration. Animals in the Rescue group displayed hearing thresholds that were significantly better than those measured in the Gentamicin or Ad.LacZ/Gentamicin groups. In the Protection group, Ad.GDNF afforded significant preservation of utricular hair cells. The data demonstrated protection of the inner ear structure, and rescue of the inner ear structure and function against ototoxic insults. These experiments suggest that inner ear gene therapy may be developed as a clinical tool for protecting the ear against environmentally induced insults.
Suzuki
M
M
Kresge Hearing Research Institute, The University of Michigan, Ann Arbor 48109-0648, USA.
Yagi
M
M
Brown
J N
JN
Miller
A L
AL
Miller
J M
JM
Raphael
Y
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005839:Gentamicins / Q000009:adverse effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D018069:Hair Cells, Vestibular / Q000187:drug effects / Q000473:pathology; D006311:Hearing Disorders / Q000139:chemically induced / Q000517:prevention & control*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes
D005839:Gentamicins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins