Bcl-2 Gene Therapy Prevents Aminoglycoside-Induced Degeneration of Auditory and Vestibular Hair Cells

被引:34
作者
Pfannenstiel, Susanna C. [1 ,3 ]
Praetorius, Mark [3 ]
Plinkert, Peter K. [3 ]
Brough, Douglas E. [2 ]
Staecker, Hinrich [1 ]
机构
[1] Univ Kansas, Dept Otolaryngol Head & Neck Surg, Sch Med, Kansas City, KS 66160 USA
[2] GenVec Inc, Gaithersburg, MD USA
[3] Univ Heidelberg, Dept Otolaryngol, Heidelberg, Germany
关键词
Adenovector; Aminoglycosides; bcl-2 gene therapy; Gentamicin; Mice; Ototoxicity; Outer hair cells; Vestibulotoxicity; INNER-EAR; IN-VIVO; MEDIATED DELIVERY; DEATH; COCHLEAR; GENTAMICIN; OTOTOXICITY; VECTOR; EXPRESSION; MOUSE;
D O I
10.1159/000192953
中图分类号
R36 [病理学]; R76 [耳鼻咽喉科学];
学科分类号
100104 ; 100213 ;
摘要
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. Copyright (C) 2009 S. Karger AG, Basel
引用
收藏
页码:254 / 266
页数:13
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