Dataset Information

Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation.

ABSTRACT: Cochlear gene therapy holds promise for the treatment of genetic deafness. Assessing its impact in adult murine models of hearing loss, however, has been hampered by technical challenges that have made it difficult to establish a robust method to deliver transgenes to the mature murine inner ear. Here in we demonstrate the feasibility of a combined round window membrane injection and semi-circular canal fenestration technique in the adult cochlea. Injection of both AAV2/9 and AAV2/Anc80L65 via this approach in P15-16 and P56-60 mice permits robust eGFP transduction of virtually all inner hair cells throughout the cochlea with variable transduction of vestibular hair cells. Auditory thresholds are not compromised. Transduction rate and cell tropism is primarily influenced by viral titer and AAV serotype but not age at injection. This approach is safe, versatile and efficient. Its use will facilitate studies using cochlear gene therapy in murine models of hearing loss over a wide range of time points.

SUBMITTER: Yoshimura H

PROVIDER: S-EPMC5812997 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation.

Yoshimura Hidekane H Shibata Seiji B SB Ranum Paul T PT Smith Richard J H RJH

Scientific reports 20180214 1

Cochlear gene therapy holds promise for the treatment of genetic deafness. Assessing its impact in adult murine models of hearing loss, however, has been hampered by technical challenges that have made it difficult to establish a robust method to deliver transgenes to the mature murine inner ear. Here in we demonstrate the feasibility of a combined round window membrane injection and semi-circular canal fenestration technique in the adult cochlea. Injection of both AAV2/9 and AAV2/Anc80L65 via t ...[more]

PMID: 29445157

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Project description:Background: The development of less traumatic surgical techniques, such as the round window approach (RWA), as well as the use of flexible electrodes and post-operative steroid administration have enabled the preservation of residual hearing after cochlear implantation (CI) surgery. However, consideration must still be given to the complications that can accompany CI. One such potential complication is the impairment of vestibular function with resulting vertigo symptoms. The aim of our current study was to examine the changes in vestibular function after implantation in patients who received CI using less traumatic surgery, particularly the RWA technique. Methods: Sixty-six patients who received CI in our center were examined by caloric testing, cervical vestibular evoked myogenic potential (cVEMP) and ocular VEMP (oVEMP) before or after implantation, or both, to obtain data on semicircular canal, saccular and utricular function, respectively. Less traumatic CI surgery was performed by the use of the RWA and insertion of flexible electrodes such as MED-EL FLEX soft, FLEX 28, and FLEX 24 (Innsbruck, Austria). Results: Caloric response and the asymmetry ratio of cVEMP and oVEMP were examined before and after implantation using less traumatic surgical techniques. Compared with before implantation, 93.9, 82.4, and 92.5% of the patients showed preserved vestibular function after implantation based on caloric testing, cVEMP and oVEMP results, respectively. We also examined the results for vestibular function by a comparison of the 66 patients using the RWA and flexible electrodes, and 17 patients who underwent cochleostomy and insertion of conventional or hard electrodes. We measured responses using caloric testing, cVEMP and oVEMP in patients after CI. There were no differences in the frequencies of abnormal caloric and oVEMP results in the implanted ears between the RWA and cochleostomy. On the other hand, the frequency of abnormal cVEMP responses in the implanted ears in the patients who received implantation by cochleostomy was significantly higher than that in the patients undergoing surgery using the RWA. Conclusion: Patients receiving CI using less traumatic surgical techniques such as RWA and flexible electrodes have reduced risk of damage to vestibular function.

Project description:ObjectiveThe aim of this study was to determine optimal radiological parameters for assessment of the round window approach in cochlear implantation surgery.Materials and methodsPatients undergoing cochlear implantation at the Department of Otolaryngology in Szczecin, between 2015 and 2022 inclusive, were eligible for the study. Radiological assessments were performed according to eight parameters (seven proposed in the literature) and visibility clinical assessments were made intra-operatively on a scale of 1 to 5 (1 - not visible, 5 - fully visible). Visibility assessments of the round window niche (RWN) and round window membrane (RWM) allowed the difference (RWN minus RWM) to be used as a clinical assessment of the size of the overhang over the round window.ResultsComputed tomography images of 57 ears from 52 patients were analyzed in terms of round window access. The study group included 26 females and 26 males, ranging in age from 1 year to 80 years, with a median age of 41 years. In clinical assessment, round window visibility was rated as 5, after removal of the bone overhang, in 69% of patients. Cochlear access through the round window was achieved in 39 (68%) cases, extended access through the round window in 13 (23%) cases and cochleostomy was performed in 5 (9%) cases. Statistically significant ordinal correlations with round-window access were found using one parameter from the literature (Chen_Angle) and from our proposal (RWM_prediction). From parameters describing the bone overhang of the round window, positive correlations (using Kendall rank tests) were found using parameters from the literature (Sarafraz_OH and Mehanna_OH).ConclusionsRadiological measurements describing access to the round window which determine the angle based on the anatomy of the posterior wall of the auditory canal and the position of the facial nerve were found to be of the highest value.Clinical relevance statementIn the future, the use of algorithms for computed tomography evaluation and robot-assisted surgery will require parameters for assessing round window access, for surgery planning and choice of electrode. The parameters proposed by various authors are summarized, allowing researchers to assess their usefulness in further clinical practice.

Dataset Information

Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation.

Publications

Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation.

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