Vector-Mediated Delivery of bcl-2 Prevents Degeneration of Auditory Hair Cells and Neurons after InjuryStaecker H. · Liu W. · Malgrange B. · Lefebvre P.P. · van De Water T.R.
aDepartment of Otolaryngology, University of Kansas, Kansas City, Kans., bDepartment of Otolaryngology, Albert Einstein College of Medicine, Bronx, N.Y., cDepartment of Otolaryngology, University of Miami School of Medicine, Miami, Fla., USA; dCenter for Cellular and Molecular Neuroscience, and eDepartment of Otolaryngology, University of Liege, Liege, Belgium
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. Conclusion: Expression of bcl-2 in cochlear tissues protects sensory cells from a variety of insults that have been demonstrated to damage the inner ear.
Hinrich Staecker MD, PhD
Department of Otolaryngology
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Received: April 7, 2003
Accepted after revision: February 9, 2006
Published online: November 2, 2006
Number of Print Pages : 8
Number of Figures : 6, Number of Tables : 0, Number of References : 27
ORL (Journal for Oto-Rhino-Laryngology and Ist Related Specialties)
Vol. 69, No. 1, Year 2007 (Cover Date: December 2006)
Journal Editor: O'Malley, B.W., Jr. (Philadelphia, Pa.)
ISSN: 0301–1569 (print), 1423–0275 (Online)
For additional information: http://www.karger.com/ORL