Mechanisms of hearing loss from trauma and inflammation: otoprotective therapies from the laboratory to the clinic.
This article reviews a series of in vitro and in vivo studies that examined the otoprotective efficacy of locally delivered dexamethasone and explored the mechanisms by which dexamethasone protects auditory hair cells. These studies used auditory threshold testing in response to pure tone stimuli, organ of Corti explant cultures, FITC-phalloidin-stained explants, and surface preparations to determine hair cell density, osmotic pump delivery of dexamethasone into the scala tympani, an animal model of electrode insertion trauma (EIT)-induced hearing loss, and real-time RT-PCR studies of gene expression levels. Local delivery of two different formulations of dexamethasone conserved hearing and protected hair cells in an animal model of cochlear implantation. Dexamethasone treatment protected hair cells in organ of Corti explants exposed to an ototoxic level of an inflammatory cytokine, and gene expression studies showed that this protection was accomplished by increased expression levels of anti-apoptosis genes (e.g. Bcl-2) and decreased levels of pro-apoptosis genes (e.g. Bax). We conclude that dexamethasone is an effective otoprotective drug for both the conservation of hearing and preservation of hair cells against trauma-induced losses. Locally delivered dexamethasone is a promising therapeutic approach for the conservation of hearing during the process of cochlear implantation.
van de Water
Thomas R
TR
Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami, Miller School of Medicine, Miami, FL 33136-1015, USA. tvandewater@med.miami.edu
Dinh
Christine T
CT
Vivero
Richard
R
Hoosien
Gia
G
Eshraghi
Adrien A
AA
Balkany
Thomas J
TJ
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000187:drug effects*; D002452:Cell Count; D019929:Cochlear Implantation / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D003638:Deafness / Q000209:etiology*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004567:Electrodes, Implanted / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D009925:Organ of Corti / Q000187:drug effects / Q000293:injuries*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D012533:Scala Tympani / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone