Investigating prestin's role in outer hair cell survival

The objective of this study is to investigate how prestin contributes to survival of outer hair cells, the outcome of which could allow development of a novel strategy to reduce hearing impairment. Prestin is the voltage-dependent molecular motor responsible for the somatic electromotility of outer hair cells (OHCs) (17). That this process is essential for sensitivity and frequency selectivity in mammals was demonstrated using mouse models lacking prestin (knockout (KO), (1, 8)) or expressing mutated prestinV499G/Y501H (referred to as “499-prestin” knockin (KI) with impaired motor function (3, 6, 16)). Quite unexpectedly, it was discovered that these mice suffer premature OHC loss, implying prestin functions not only for cochlear amplification but also for OHC survival. We hypothesize that prestin’s voltagedependent motor activity is also used as a “shock absorber” to alleviate mechanical stress imposed on OHCs, which is exacerbated by their attachment to the tectorial membrane (TM), and that the OHC death seen in prestin-KO and 499-prestin-KI mice is ascribed to the loss of this shock-absorbing function. Our hypothesis stems from the following preliminary data.