アポトーシス抑制タンパク PTD-FNKを用いた内耳タンパク治療についての研究

学位の種別:論文博士University of Tokyo(東京大学

The Hearing Outcomes of Cochlear Implantation in Waardenburg Syndrome

Objectives. This study aimed to determine the feasibility of cochlear implantation for sensorineural hearing loss in patients with Waardenburg syndrome. Method. A retrospective chart review was performed on patients who underwent cochlear implantation at the University of Tokyo Hospital. Clinical classification, genetic mutation, clinical course, preoperative hearing threshold, highresolution computed tomography of the temporal bone, and postoperative hearing outcome were assessed. Result. Five children with Waardenburg syndrome underwent cochlear implantation. The average age at implantation was 2 years 11 months (ranging from 1 year 9 months to 6 years 3 months). Four patients had congenital profound hearing loss and one patient had progressive hearing loss. Two patients had an inner ear malformation of cochlear incomplete partition type 2. No surgical complication or difficulty was seen in any patient. All patients showed good hearing outcome postoperatively. Conclusion. Cochlear implantation could be a good treatment option for Waardenburg syndrome

Accepted Manuscript Title: Hydrogen in drinking water attenuates noise-induced hearing loss in guinea pigs

A c c e p t e d M a n u s c r i p t Hydrogen in drinking water reduced ABR threshold shifts after noise exposure. Hydrogen attenuated a decrease of DPOAE amplitudes after noise exposure. Hydrogen facilitated the recovery of hair cell function after noise. Hydrogen attenuated noise-induced temporary hearing loss. *Research Highlights Page 2 of 16 A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t Abstract It has been shown that molecular hydrogen acts as a therapeutic and preventive antioxidant by selectively reducing the hydroxyl radical, the most cytotoxic of the reactive oxygen species. In the present study, we tested the hypothesis that acoustic damage in guinea pigs can be attenuated by the consumption of molecular hydrogen. Guinea pigs received normal water or hydrogen-rich water for 14 days before they were exposed to 115 dB SPL 4-kHz octave band noise for 3 h. Animals in each group underwent measurements for auditory brainstem response (ABR) or distortion-product otoacoustic emissions (DPOAEs) before the treatment (baseline) and immediately, 1, 3, 7, and 14 days after noise exposure. The ABR thresholds at 2 and 4 kHz were significantly better on post-noise day 1, 3, and 14 in hydrogen-treated animals when compared to the normal water-treated controls. Compared to the controls, the hydrogen-treated animals showed greater amplitude of DPOAE input/output growth functions during the recovery process, with statistical significance detected on post-noise days 3 and 7. These findings suggest that hydrogen can facilitate the recovery of hair cell function and attenuate noise-induced temporary hearing loss

Cochlear implantation for hearing loss due to an A8296G mitochondrial DNA mutation

Objective: To characterize the clinical findings in a patient with hearing loss harboring an A8296G mitochondrial DNA mutation and the outcome of cochlear implantation. Patients: A case report of a patient with hearing loss caused by an A8296G mitochondrial DNA mutation. Intervention: The patient underwent cochlear implantation (CI).Main outcome and results: Bilateral moderate to severe hearing loss was found at high school age and progressed to severe hearing loss bilaterally at the age of 22. The patient's low-tone hearing was relatively well preserved compared to high frequency, although it eventually declined. Speech perception in silence and at S/N10 improved to 100% and 92% for sentences, respectively, 3 years after CI. Conclusions: We detailed the case of a patient with hearing loss due to an A8296G mitochondrial DNA mutation. Bilateral progressive hearing loss starting from high frequency was observed. Speech discrimination after CI was very good, indicating that a patient with this mutation is a good candidate for CI. Keywords: Mitochondrial DNA mutation, Hearing loss, Cochlear implantatio

Age-Related Hearing Loss in Mn-SOD Heterozygous Knockout Mice

Age-related hearing loss (AHL) reduces the quality of life for many elderly individuals. Manganese superoxide dismutase (Mn-SOD), one of the antioxidant enzymes acting within the mitochondria, plays a crucial role in scavenging reactive oxygen species (ROS). To determine whether reduction in Mn-SOD accelerates AHL, we evaluated auditory function in Mn-SOD heterozygous knockout (HET) mice and their littermate wild-type (WT) C57BL/6 mice by means of auditory brainstem response (ABR). Mean ABR thresholds were significantly increased at 16 months when compared to those at 4 months in both WT and HET mice, but they did not significantly differ between them at either age. The extent of hair cell loss, spiral ganglion cell density, and thickness of the stria vascularis also did not differ between WT and HET mice at either age. At 16 months, immunoreactivity of 8-hydroxydeoxyguanosine was significantly greater in the SGC and SV in HET mice compared to WT mice, but that of 4-hydroxynonenal did not differ between them. These findings suggest that, although decrease of Mn-SOD by half may increase oxidative stress in the cochlea to some extent, it may not be sufficient to accelerate age-related cochlear damage under physiological aging process

Exploring the Source of Neural Responses of Different Latencies Obtained from Different Recording Electrodes in Cochlear Implant Users

In this study we measured the electrically evoked compound action potential (ECAP) from different recording electrodes in the cochlea. Under the assumption that different response latencies may be the result of differences in the neural population contributing to the response, we assessed the relationship between neural response latency and spread of excitation. First, we evaluated changes in N1 latency when the recording electrode site was varied. Second, we recorded channel interaction functions using a forward masking technique but with recording electrodes at different intracochlear locations. For most individuals, N1 latency was similar across recording electrodes. However, reduced N1 latencies were observed in 21% of cochlear implant users when ECAPs were recorded using a remote recording electrode. We hypothesized that if recordings from different electrodes represented contributions from different populations of neurons, then one might expect that channel interaction functions would be different. However, we did not observe consistent differences in channel interaction functions (neither peak location nor breadth of the functions), and further, any variation in channel interaction functions was not correlated with ECAP latency. These results suggest that ECAPs from different recording electrodes with different latencies originate from similar neural populations

Hydrogen in drinking water attenuates noise-induced hearing loss in guinea pigs

a b s t r a c t It has been shown that molecular hydrogen acts as a therapeutic and preventive antioxidant by selectively reducing the hydroxyl radical, the most cytotoxic of the reactive oxygen species. In the present study, we tested the hypothesis that acoustic damage in guinea pigs can be attenuated by the consumption of molecular hydrogen. Guinea pigs received normal water or hydrogen-rich water for 14 days before they were exposed to 115 dB SPL 4-kHz octave band noise for 3 h. Animals in each group underwent measurements for auditory brainstem response (ABR) or distortion-product otoacoustic emissions (DPOAEs) before the treatment (baseline) and immediately, 1, 3, 7, and 14 days after noise exposure. The ABR thresholds at 2 and 4 kHz were significantly better on post-noise days 1, 3, and 14 in hydrogen-treated animals when compared to the normal water-treated controls. Compared to the controls, the hydrogen-treated animals showed greater amplitude of DPOAE input/output growth functions during the recovery process, with statistical significance detected on post-noise days 3 and 7. These findings suggest that hydrogen can facilitate the recovery of hair cell function and attenuate noise-induced temporary hearing loss