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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

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

doi: 10.1097/MAO.0b013e3181859a1f
Basic Sciences
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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.

Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami, Miller School of Medicine, Miami, Florida, U.S.A.

Address correspondence and reprint requests to Thomas R. Van De Water, Ph.D., Cochlear Implant Research Program, University of Miami Ear Institute, 1600 NW 10th Avenue, RMSB 3160, Miami, FL 33136-1015, U.S.A.; E-mail: tvandewater@med.miami.edu

Research supported by a grant from Advanced Bionics Corporation, Valencia, CA, U.S.A.

© 2008 Otology & Neurotology, Inc.