Gentamicin Ototoxicity Requires Functional Mechanotransducer Channels

Abstract

ORAL PRESENTATIONSdecompression surgery are low risk of hearing impediment and long effective period after onset of paralysis.Objective: Test the hypothesis that open mechanotransducer (MET) channels are required for aminoglycoside entry and toxicity in auditory hair cells.Method: Cochlear cultures from postnatal 4-day-old rats were treated with gentamicin with and without MET channel blockers. The effects of MET channel blockers on hair cell survival were assessed by cell counts after immunohistochemistry. Two-photon imaging was used to quantify uptake of TexasRed-conjugated gentamicin (GTTR) into live hair cells.Results: Gentamicinalone (0.1mM) caused 76.5% hair cell loss in the basal cochlear turn. Cotreatment with MET channel blockers, 1.0 mM curare, and 0.5 mM quinine conferred protection (0.4% and 7.4% hair cell loss, both P < .001); whereas treatment with endocytosis inhibitors, 2.6 µM conconavalin A and 80 µM dynosore, did not (63.7% and 76.0% hair cell loss). Two-photon imaging showed that GTTR uptake (3 µM) into live hair cells was rapid and selective. Quinine and curare, but not concanavalin A, reduced GTTR uptake. Furthermore, as low calcium increases the open probability of MET channels, hypocalcemia showed facilitated GTTR uptake.Conclusion: Functional MET channels are required for aminoglycoside uptake into hair cells and its toxicity. Results suggest that limiting permeation of aminoglycosides through MET channels is a potential therapeutic target for preventing hair cell death. Otology/Neurotology Habituation following Tinnitus Retraining Therapy in Tinnitus SufferersJiun Fong Thong (presenter); Mei Ching Wong; S. Junaidah; Yew Meng Chan, FRCS Objective: Evaluate the efficacy of Tinnitus Retraining Therapy (TRT) in habituating patients with tinnitus.Method: Prospective study of patients presenting to the tinnitus clinic at a tertiary referral otorhinolaryngology unit in Singapore over a 13-year period (1997 to 2010). Patients who underwent Tinnitus Retraining therapy were followed up with structured interviews with the aid of questionnaire forms. Habituation following TRT was evaluated.Results: A total of 702 patients were studied (55% male, 45% female). Average age was 51 years. Habituation of reaction to tinnitus and habituation of perception were analyzed. Average duration of follow-up was 33 months (range, 0.25-151 months). A total of 68% of patients described improvement in annoyance following TRT. Of these, 80% described habituation of perception as well. There was no statistical difference in gender and age between patients who did and did not respond to TRT. However, duration of treatment was significantly longer in patients who habituated. Conclusion:The goal of TRT is to achieve habituation of reaction to tinnitus. Habituation of perception is often a secondary result of sufficiently habituated response. From our study, more than two-thirds of patients with tinnitus achieved habituation of reaction, and of these, the majority also habituated to awareness of the tinnitus. Otology/Neuroto...

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