Biopolymer-released dexamethasone prevents tumor necrosis factor α-induced loss of auditory hair cells in vitro: Implications toward the development of a drug-eluting cochlear implant electrode array

Christine Dinh, Kimberly Hoang, Scott Haake, Shibing Chen, Simon Angeli, Eva Nong, Adrien A. Eshraghi, Thomas J. Balkany, Thomas R. Van De Water

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Hypothesis: Polymer-eluted dexamethasone (DXM) will retain its ability to protect against tumor necrosis factor α (TNFα)-induced hair cell (HC) loss. Background: TNFα has been shown to be associated with trauma-induced hearing loss. DXM has been demonstrated to protect the cochlea against trauma-induced hearing loss. DXM is currently administered either systemically or locally to treat patients with sudden hearing loss of unknown cause. Methods: P-3 organ of Corti explants challenged with an ototoxic level of TNFα was the experimental system, and the base form of DXM (DXMb) incorporated into a biorelease polymer (i.e., SIBS) was the otoprotection molecule tested. The efficacy of otoprotection was determined by counts of fluorescein isothiocyanate-phalloidin-stained HCs and changes in gene expression. Results: HC counts show 1) SIBS alone did not protect HCs from TNFα ototoxicity (SIBS versus SIBS + TNFα; p < 0.001), and 2) SIBS with DXMb provides a significant level of protection against TNFα-induced loss of HCs (TNFα + SIBS versus TNFα + SIBS/DXMb, 299 μg; p < 0.001). Gene expression results show that polymer-eluted DXMb 1) upregulates antiapoptotic genes (i.e., Bcl-2, Bcl-xl) and downregulates a proapoptotic gene (i.e., Bax) in TNFα-challenged explants and 2) downregulates TNFR1 in these explants. Conclusion: Polymer-eluted DXMb retains its otoprotection capabilities in our in vitro test system of TNFα-challenged organ of Corti explants by altering the pattern of gene expression to favor survival of TNFα-exposed HCs. These results, although in vitro, support the application of polymer containing DXMb to electrode arrays for the conservation of hearing during cochlear implantation.

Original languageEnglish (US)
Pages (from-to)1012-1019
Number of pages8
JournalOtology and Neurotology
Volume29
Issue number7
DOIs
StatePublished - Dec 1 2008

Keywords

  • Cochlear implantation
  • Drug delivery
  • Glucocorticoid
  • Inflammatory cytokine
  • Otoprotection
  • Trauma-induced hair cell loss

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Clinical Neurology
  • Sensory Systems
  • Medicine(all)

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