| 1. |
- Liu, Wei, et al.
(author)
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Expression of trans-membrane serine protease 3 (TMPRSS3) in the human organ of Corti
- 2018
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In: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 372:3, s. 445-456
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Journal article (peer-reviewed)abstract
- TMPRSS3 (Trans-membrane Serine Protease 3) is a type II trans-membrane serine protease that has proteolytic activity essential for hearing. Mutations in the gene cause non-syndromic autosomal recessive deafness (DFNB8/10) in humans. Knowledge about its cellular distribution in the human inner ear may increase our understanding of its physiological role and involvement in deafness, ultimately leading to therapeutic interventions. In this study, we used super-resolution structured illumination microscopy for the first time together with transmission electron microscopy to localize the TMPRSS3 protein in the human organ of Corti. Archival human cochleae were dissected out during petroclival meningioma surgery. Microscopy with Zeiss LSM710 microscope achieved a lateral resolution of approximately 80 nm. TMPRSS3 was found to be associated with actin in both inner and outer hair cells. TMPRSS3 was located in cell surface-associated cytoskeletal bodies (surfoskelosomes) in inner and outer pillar cells and Deiters cells and in subcuticular organelles in outer hair cells. Our results suggest that TMPRSS3 proteolysis is linked to hair cell sterociliary mechanics and to the actin/microtubule networks that support cell motility and integrity.
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| 2. |
- Maier, Hannes, et al.
(author)
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Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss
- 2022
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In: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
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Journal article (peer-reviewed)abstract
- Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
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| 3. |
- Sahaboglu, Ayse, et al.
(author)
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PARP1 Gene Knock-Out Increases Resistance to Retinal Degeneration without Affecting Retinal Function
- 2010
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11
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Journal article (peer-reviewed)abstract
- Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation of enzymes belonging to the poly-ADP-ribose polymerase (PARP) group was shown to be involved in photoreceptor degeneration in the human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated the exact relevance of the predominant isoform - PARP1 - for photoreceptor cell death using PARP1 knock-out (KO) mice. In vivo and ex vivo morphological analysis using optic coherence tomography (OCT) and conventional histology revealed no major alterations of retinal phenotype when compared to wild-type (wt). Likewise, retinal function as assessed by electroretinography (ERG) was normal in PARP1 KO animals. We then used retinal explant cultures derived from wt, rd1, and PARP1 KO animals to test their susceptibility to chemically induced photoreceptor degeneration. Since photoreceptor degeneration in the rd1 retina is triggered by a loss-of-function in phosphodiesterase-6 (PDE6), we used selective PDE6 inhibition to emulate the rd1 situation on non-rd1 genotypes. While wt retina subjected to PDE6 inhibition showed massive photoreceptor degeneration comparable to rd1 retina, in the PARP1 KO situation, cell death was robustly reduced. Together, these findings demonstrate that PARP1 activity is in principle dispensable for normal retinal function, but is of major importance for photoreceptor degeneration under pathological conditions. Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP.
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| 4. |
- Senn, Pascal, et al.
(author)
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NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons
- 2017
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In: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 38:8, s. E224-E231
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Journal article (peer-reviewed)abstract
- Cochlear implants (CI) restore functional hearing in the majority of deaf patients. Despite the tremendous success of these devices, some limitations remain. The bottleneck for optimal electrical stimulation with CI is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear. As a consequence, current devices are limited through 1) low frequency resolution, hence suboptimal sound quality and 2), large stimulation currents, hence high energy consumption (responsible for significant battery costs and for impeding the development of fully implantable systems). A recently completed, multinational and interdisciplinary project called NANOCI aimed at overcoming current limitations by creating a gapless interface between auditory nerve fibers and the cochlear implant electrode array. This ambitious goal was achieved in vivo by neurotrophin-induced attraction of neurites through an intra-cochlear gel-nanomatrix onto a modified nanoCI electrode array located in the scala tympani of deafened guinea pigs. Functionally, the gapless interface led to lower stimulation thresholds and a larger dynamic range in vivo, and to reduced stimulation energy requirement (up to fivefold) in an in vitro model using auditory neurons cultured on multi-electrode arrays. In conclusion, the NANOCI project yielded proof of concept that a gapless interface between auditory neurons and cochlear implant electrode arrays is feasible. These findings may be of relevance for the development of future CI systems with better sound quality and performance and lower energy consumption. The present overview/review paper summarizes the NANOCI project history and highlights achievements of the individual work packages.
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