Hongzheng Zhang1, Gemaine Stark, Lina Reiss. 1. *Department of Otolaryngology Head & Neck Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, China; and †Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health and Science University, Portland, Oregon, U.S.A.
Abstract
HYPOTHESIS: Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation. BACKGROUND: Between 30 and 50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes. METHODS: Guinea pigs were implanted in one ear with cochlear implant electrode arrays, with non-implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14 days. Hearing threshold changes were measured over time. Cochlear ribonucleic acid was analyzed using real-time quantitative reverse transcription-polymerase chain reaction from the following gene families: cytokines, tight junction claudins, ion and water (aquaporin) transport channels, gap junction connexins, and tissue remodeling genes. RESULTS: Significant increases in expression were observed for cochlear inflammatory genes (Cxcl1, IL-1β, TNF-α, and Tnfrsf1a/b) and ion homeostasis genes (Scnn1γ, Aqp3, and Gjb3). Upregulation of tissue remodeling genes (TGF-β, MMP2, MMP9) as well as a paracrine gene (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with some recovery at 7 and 14 days after implantation. MM9 exhibited extreme upregulation of expression and was qualitatively associated with changes in hearing thresholds. CONCLUSION: Cochlear implantation induces similar changes as middle ear inflammation for genes involved in inflammation and ion and water transport function, whereas tissue remodeling changes differ markedly. The upregulation of MMP9 with hearing loss is consistent with previous findings linking stria vascularis vessel changes with cochlear implant-induced hearing loss.
HYPOTHESIS: Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation. BACKGROUND: Between 30 and 50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes. METHODS:Guinea pigs were implanted in one ear with cochlear implant electrode arrays, with non-implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14 days. Hearing threshold changes were measured over time. Cochlear ribonucleic acid was analyzed using real-time quantitative reverse transcription-polymerase chain reaction from the following gene families: cytokines, tight junction claudins, ion and water (aquaporin) transport channels, gap junction connexins, and tissue remodeling genes. RESULTS: Significant increases in expression were observed for cochlear inflammatory genes (Cxcl1, IL-1β, TNF-α, and Tnfrsf1a/b) and ion homeostasis genes (Scnn1γ, Aqp3, and Gjb3). Upregulation of tissue remodeling genes (TGF-β, MMP2, MMP9) as well as a paracrine gene (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with some recovery at 7 and 14 days after implantation. MM9 exhibited extreme upregulation of expression and was qualitatively associated with changes in hearing thresholds. CONCLUSION: Cochlear implantation induces similar changes as middle ear inflammation for genes involved in inflammation and ion and water transport function, whereas tissue remodeling changes differ markedly. The upregulation of MMP9 with hearing loss is consistent with previous findings linking stria vascularis vessel changes with cochlear implant-induced hearing loss.
Authors: Douglas C Fitzpatrick; Adam P Campbell; Adam T Campbell; Baishakhi Choudhury; Margaret T Dillon; Margaret P Dillon; Mathieu Forgues; Craig A Buchman; Oliver F Adunka Journal: Otol Neurotol Date: 2014-01 Impact factor: 2.311
Authors: T Sobue; T Gravely; A Hand; Y K Min; C Pilbeam; L G Raisz; X Zhang; D Larocca; R Florkiewicz; M M Hurley Journal: J Bone Miner Res Date: 2002-03 Impact factor: 6.741
Authors: Thomas R van de Water; Christine T Dinh; Richard Vivero; Gia Hoosien; Adrien A Eshraghi; Thomas J Balkany Journal: Acta Otolaryngol Date: 2010-03 Impact factor: 1.494
Authors: Bruce J Gantz; Marlan R Hansen; Christopher W Turner; Jacob J Oleson; Lina A Reiss; Aaron J Parkinson Journal: Audiol Neurootol Date: 2009-04-22 Impact factor: 1.854
Authors: Elizabeth A Dugan; Cassie Bennett; Ilmar Tamames; W Dalton Dietrich; Curtis S King; Abhishek Prasad; Suhrud M Rajguru Journal: J Neural Eng Date: 2020-04-29 Impact factor: 5.379
Authors: Ye Ji Shim; Byung Yoon Choi; Kyo Hoon Park; Hyunju Lee; Young Mi Jung; Yu Mi Kim Journal: Mediators Inflamm Date: 2018-09-19 Impact factor: 4.711
Authors: Lukas D Landegger; Sasa Vasilijic; Takeshi Fujita; Vitor Y Soares; Richard Seist; Lei Xu; Konstantina M Stankovic Journal: Front Neurol Date: 2019-09-11 Impact factor: 4.003
Authors: Alexander D Claussen; René Vielman Quevedo; Brian Mostaert; Jonathon R Kirk; Wolfram F Dueck; Marlan R Hansen Journal: PLoS One Date: 2019-04-18 Impact factor: 3.240