Changes in Gene Expression and Hearing Thresholds after Cochlear Implantation

Hongzheng Zhang, Gemaine Stark, Lina Reiss

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1157-1165
Number of pages9
JournalOtology and Neurotology
Volume36
Issue number7
DOIs
StatePublished - Aug 27 2015

Fingerprint

Cochlear Implantation
Hearing
Gene Expression
Hearing Loss
Cochlear Implants
Genes
Acoustic Stimulation
Up-Regulation
Cochlea
Ear
Claudins
Ions
Stria Vascularis
Inflammation
Aquaporins
Connexins
Water
Tight Junctions
Gap Junctions
Ion Transport

Keywords

  • Cochlear implants
  • Electro-acoustic stimulation
  • Gene expression
  • Guinea pig model
  • Hearing loss
  • Inflammation response
  • Ion homeostasis
  • Tissue remodeling

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Clinical Neurology
  • Sensory Systems

Cite this

Changes in Gene Expression and Hearing Thresholds after Cochlear Implantation. / Zhang, Hongzheng; Stark, Gemaine; Reiss, Lina.

In: Otology and Neurotology, Vol. 36, No. 7, 27.08.2015, p. 1157-1165.

Research output: Contribution to journalArticle

Zhang, Hongzheng ; Stark, Gemaine ; Reiss, Lina. / Changes in Gene Expression and Hearing Thresholds after Cochlear Implantation. In: Otology and Neurotology. 2015 ; Vol. 36, No. 7. pp. 1157-1165.
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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.",
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AB - 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.

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