Cochlear origin of tinnitus and outer hair cell motor protein Prestin as a biomarker for tinnitus

Abstract

Peripheral dysfunction and hearing loss are known risk factors for tinnitus; however, a portion of tinnitus patients exhibit no apparent peripheral auditory deficits. This article proposes that tinnitus may originate in the cochlea due to, undetectable damage to outer hair cells (OHCs) in individuals with normal hearing. The study further suggests that peripheral auditory deficits can be identified through the outer hair cell motor protein Prestin, which has potential as a biomarker for early detection. Minor OHC losses, which do not result in clinically detectable hearing loss, may lead to insufficient depolarization of inner hair cells (IHCs), thereby reducing sensory input along the cochlea-cortex pathway in the central auditory system. From a homeostatic gain control perspective, decreased amplification by OHCs, including abnormal electromotile responses, may lead to inadequate encoding by IHCs, contributing to the cochlear origin of tinnitus. Damage to OHCs that does not affect hearing thresholds, or abnormal electromotile contractions influenced by Prestin, may contribute to peripheral auditory dysfunction underlying tinnitus. As a result, pre-neural mismatched synchronization between OHCs and IHCs, driven by abnormal OHC electromotility, could cause sound processing disorders within the central auditory system. This pathophysiological mechanism at the cochlear level may lead to pathological alterations at multiple levels of the central auditory system. Prestin may serve as a potential biomarker for tinnitus, offering valuable insights into its cochlear origin and guiding future therapeutic developments.