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J. Otorhinolaryngol. Hear. Balance Med. 2018, 1(1), 2; doi:10.3390/ohbm1010002

Effects of Retinoid Treatment on Cochlear Development, Connexin Expression and Hearing Thresholds in Mice

Department of Otolaryngology, Emory University School of Medicine, 615 Michael Street, Room# 543, Atlanta, GA 30322-3030, USA
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Received: 5 July 2017 / Revised: 10 August 2017 / Accepted: 17 October 2017 / Published: 23 October 2017
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Abstract

Mutations in GJB2, gene coding for connexin 26 (Cx26), and GJB6, gene coding for connexin 30 (Cx30), are the most common genetic defects causing non-syndromic hereditary hearing loss. We previously reported that overexpression of Cx26 completely rescues the hearing in a mouse model of human GJB6 null mutations. The results suggest that therapeutic agents up-regulating the expression of Cx26 may potentially be a novel treatment for non-syndromic hereditary deafness caused by Cx30 null mutations. Retinoids are a family of vitamin A derivatives that exert broad and profound effects on cochlear protein expression including connexins. They are readily available and already utilized as therapeutic agents for recurrent otitis media and hearing loss due to noise exposure. In this study, we characterized the expression of Cx26 and Cx30 in the postnatal inner ear by different retinoids including retinyl palmitate (RP), the main source of vitamin A in over-the-counter (OTC) supplements, retinyl acetate (RAc) which is an isomer of RP, and all-trans-retinoic acid (ATRA), the most active retinoid derivative. The results revealed ATRA significantly increased cochlear Cx26 expression and improved hearing in Cx30 knockout (KO) mice by 10 dB suggesting its potential benefits as a therapeutic agent. In contrast, RP selectively reduced cochlear Cx30 expression and did not improve hearing thresholds at the dosages we tested. View Full-Text
Keywords: regulation of connexin expressions; Cx26 and Cx30; retinoids; drug; hearing restoration regulation of connexin expressions; Cx26 and Cx30; retinoids; drug; hearing restoration
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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    Description: Surgical placement of gel foam soaked in vitamin A derivative was done by opening up the tympanic ring and exposing the RW. Posterior to the above photograph is the RW (indicated by a white arrow) where the placement of the gel foam occurred.

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Kim, Y.; Lin, X. Effects of Retinoid Treatment on Cochlear Development, Connexin Expression and Hearing Thresholds in Mice. J. Otorhinolaryngol. Hear. Balance Med. 2018, 1, 2.

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J. Otorhinolaryngol. Hear. Balance Med. EISSN 2504-463X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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