Spiral ganglion neurons are protected from degeneration by GDNF gene therapy.
Perceptual benefits from the cochlear prosthesis are related to the quantity and quality of the patient's auditory nerve population. Multiple neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have been shown to have important roles in the survival of inner ear auditory neurons, including protection of deafferented spiral ganglion cells (SGCs). In this study, GDNF gene therapy was tested for its ability to enhance survival of SGCs after aminoglycoside/diuretic-induced insult that eliminated the inner hair cells. The GDNF transgene was delivered by adenoviral vectors. Similar vectors with a reporter gene (lacZ) insert served as controls. Four or seven days after bilateral deafening, 5 microl of an adenoviral suspension (Ad-GDNF or Ad-lacZ) or an artificial perilymph was injected into the left scala tympani of guinea pigs. Animals were sacrificed 28 days after deafening and their inner ears prepared for SGC counts. Adenoviral-mediated GDNF transgene expression enhanced SGC survival in the left (viral-treated) deafened ears. This observation suggests that GDNF is one of the survival factors in the inner ear and may help maintain the auditory neurons after insult. Application of GDNF and other survival factors via gene therapy has great potential for inducing survival of auditory neurons following hair cell loss.
Yagi
M
M
Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506, USA.
Kanzaki
S
S
Kawamoto
K
K
Shin
B
B
Shah
P P
PP
Magal
E
E
Sheng
J
J
Raphael
Y
Y
D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003638:Deafness / Q000473:pathology / Q000628:therapy; D005347:Fibroblasts / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006168:Guinea Pigs; D009410:Nerve Degeneration / Q000517:prevention & control*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins