Vector-mediated delivery of bcl-2 prevents degeneration of auditory hair cells and neurons after injury.
OBJECTIVE
To test the hypothesis that bcl-2 prevents oxidative stress-induced apoptosis of auditory sensory cells in explants of the organ of Corti and dissociated cell cultures of the spiral ganglion.


METHODS
Organ of Corti explants and dissociated spiral ganglion cell cultures obtained from 3-day-old (P3) rats or adult spiral ganglion cell cultures from 28-day-old (P28) rats were transduced with vectors containing a human bcl-2 gene. Cultures were then exposed to neomycin, cisplatin or subjected to withdrawal of neurotrophin supplementation. Outcome measures included hair cell and neuron counts, mitochondrial membrane potential and a histological measure of apoptosis.


RESULTS
Expression of bcl-2 in the organ of Corti explants and neuronal cell cultures provided a significant level of protection against cell death. Bcl-2 expression in the organ of Corti explants also protected mitochondria from loss of membrane potential and blocked an early step in the commitment of hair cells to apoptosis.


CONCLUSIONS
Expression of bcl-2 in cochlear tissues protects sensory cells from a variety of insults that have been demonstrated to damage the inner ear.
Staecker
Hinrich
H
Department of Otolaryngology, University of Kansas, Kansas City, Kans 66160, USA. hstaecker@kumc.edu
Liu
Wei
W
Malgrange
Brigitte
B
Lefebvre
Philippe P
PP
Van De Water
Thomas R
TR
D000256:Adenoviridae; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D019254:Genes, bcl-2 / Q000502:physiology*; D005822:Genetic Vectors; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D009355:Neomycin / Q000633:toxicity; D009410:Nerve Degeneration / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor; D009355:Neomycin; D002945:Cisplatin