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Tinnitus is a poorly understood but common complaint that can have a substantial negative impact on the health and quality of life of sufferers. Risk factors for tinnitus include age, gender, noise, ototoxic drug exposure and infection. Understanding the mechanisms that underlie tinnitus and consequently development of effective treatment strategies has been hampered by lack of biomarkers and objective measures of tinnitus. Several developments have led us to this innovative proposal to develop a blood-based biomarker for tinnitus based on outer-hair-cell-specific protein, prestin. First, in salicylate models of tinnitus, prestin expression is increased in the cochlea - specifically in the outer hair cells (OHC). This suggests that upregulated prestin expression may be a contributing factor to development of tinnitus. Second, our group has demonstrated that prestin, which is an OHC-specific protein, is present and measurable in the blood and conveys meaningful information about cochlear gain and other dimensions of hearing. Third, our group has provided evidence that serum prestin levels serve as a measure of cochlear gain, both through a significant correlation with otoacoustic emissions, and a graded relationship between serum prestin levels and environmental sound levels, where higher daily sound levels correlated with lower serum prestin levels and therefore lower gain. Fourth, our latest study found that prestin levels are significantly elevated in tinnitus subjects. This result implicates OHCs in the generation of tinnitus, presumably through changes in prestin expression that result in altered electromechanical force generation in the cochlea, i.e., altered cochlear amplification. Based on these developments, we hypothesize that serum prestin levels are associated with tinnitus severity. To test this hypothesis, we propose an observational clinical trial where we recruit chronic tinnitus sufferers and obtain serial measurements of prestin to evaluate whether serum levels correlate with severity of tinnitus symptoms. If a relationship exists, the hypothesis is strengthened while establishing clear potential for prestin as a clinical biomarker for tinnitus, offering a novel tool for investigating the mechanisms of tinnitus generation.
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