Bcl-2 gene therapy prevents aminoglycoside-induced degeneration of auditory and vestibular hair cells.
To evaluate the protective effects of bcl-2, we have developed an in vivo model of gentamicin ototoxicity in C57BL/6 mice using intratympanic delivery of gentamicin. Hair cell survival was evaluated using myosin VIIa immunohistochemistry, cytocochleogram and auditory brainstem response (ABR) testing. At 10 days after gentamicin application, a consistent loss of outer hair cells was seen. Mice were pretreated with an adenovector expressing human bcl-2 (Ad.11D.bcl-2) or a control vector (Ad.11D). Seventy-two hours after vector delivery mice were treated with intratympanic gentamicin and evaluated at 10 days after ototoxin delivery. Pretreatment with Ad.11D.bcl-2 resulted in morphologic protection of hair cells and preservation of hearing thresholds measured by ABR.
Pfannenstiel
Susanna C
SC
Department of Otolaryngology Head and Neck Surgery, University of Kansas, School of Medicine, Kansas City, Kans. 66160, USA.
Praetorius
Mark
M
Plinkert
Peter K
PK
Brough
Douglas E
DE
Staecker
Hinrich
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001309:Auditory Threshold; D002470:Cell Survival; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005839:Gentamicins / Q000633:toxicity*; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism / Q000473:pathology; D018069:Hair Cells, Vestibular / Q000378:metabolism / Q000473:pathology; D006311:Hearing Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D019253:Proto-Oncogene Proteins c-bcl-2; D009218:Myosins