Otolaryngology: Open Access
Open Access

Abstract

Humans require outer hair cell (OHC)-associated amplification for their high sensitivity and sharp frequency selectivity. Unfortunately, OHC loss is involved in a majority of sensorineural hearing loss because OHCs are extremely sensitive to aging, acoustic trauma, antibiotics and chemotherapeutic drugs. The key function of OHCs is primarily carried out by OHCs? unique motor protein called prestin. It is known that cholesterol amounts in the plasma membrane of OHCs influence prestin?s function. Recently, hydroxypropyl β-cyclodextrin (HP CD) was used to treat patients of Niemann-Pick disease type C1, a fatal genetic disease characterized by a failure to metabolize and dispose of cholesterol and lipids. It was discovered that HPβCD induced hearing loss in mice. Because OHCs seem to be the only cells affected by this cholesterol-chelating agent, we wondered if this vulnerability might depend on prestin, which is only expressed in OHCs. Our data show that prestin directly binds to cholesterol in vitro. It is, therefore, conceivable that OHC death in response to cholesterol manipulation may result from disruption of the cholesterol-prestin interaction. In order to investigate this possibility, we treated wild-type and prestinknockout (KO) mice with HPβCD and analyzed their organs of Corti using immunofluorescence microscopy on cochlear whole-mount preparations. Consistent with the report by Crumling and colleagues, extensive OHC death was observed in wild-type mice. In contrast, OHCs from prestin KO mice were preserved. This observation suggests that a prestin-dependent mechanism underlies HPβCD ototoxicity.

Biography

Jing Zheng is an Associate Professor in the Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine of Northwestern University. She also holds joint appointments in the Interdepartmental Neurosciences Program and Department of Communication Sciences and Disorders. She is a Fellow of the Hugh Knowles Center for Hearing Research. She received her PhD degree from Michigan State University, USA. She has published more than 40 papers in peerreviewed research journals and serving as Editorial Board Members for several journals.