Hair cell loss in the organ of Corti is the most common cause of permanent sensorineural deafness. In contrast to mammals, birds have been shown to recover both structurally and functionally from injury to the inner ear epithelium. Supporting cells which surround the sensory hair cells have been shown to play an important roll in maintaining the injured epithelium. In mammals these supporting cells create scars that repair the tissue and in birds they generate new hair cells. The goal of this proposal is to understand mechanisms of repair in the auditory epithelia of mammals and birds and to elucidate the differences between these repair mechanisms. Our first specific aim is to examine the response of the auditory epithelium to trauma in mammals. Specifically, we will study changes induced by trauma in tissue distribution of molecules that are involved in signaling, and localize organelles responsible for tissue organization. In parallel to these studies in mammals, our second specific aim analyzes repair and regeneration in the avian auditory epithelium, to determine the cellular and molecular regulation of avian supporting cell response to injury. specifically, we will correlate regenerative activity of supporting cells with their morphology, characterize conversion of supporting cells into hair cells, localize signaling molecules, and determine the spatial-temporal distribution of a parathyroid hormone-like protein and a GTP-binding protein called CDC42, 2 gene products that are preferentially expressed in supporting cells after injury of the basilar papilla. Our third specific aim is to influence the outcome of trauma to the mammalian organ of Corti, with the ultimate goal of reducing or reversing injury. For this purpose, we will use topical conditioned culture media and purified bio-active agents to influence epithelial repair. The long term goal of our research work is to induce regeneration in the mammalian auditory epithelium. We expect that the localization of gene products activated by trauma, the comparative analysis between birds and mammals, and the utilization of data and research tools from other biological systems should enable us to develop clinically relevant procedures for prevention and therapy of deafness.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Hearing Research Study Section (HAR)
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Devare, Jenna; Gubbels, Samuel; Raphael, Yehoash (2018) Outlook and future of inner ear therapy. Hear Res 368:127-135
Wang, Guo-Peng; Basu, Ishani; Beyer, Lisa A et al. (2017) Severe streptomycin ototoxicity in the mouse utricle leads to a flat epithelium but the peripheral neural degeneration is delayed. Hear Res 355:33-41
Fukui, Hideto; Raphael, Yehoash (2013) Gene therapy for the inner ear. Hear Res 297:99-105
Jung, Jae Yun; Avenarius, Matt R; Adamsky, Swetlana et al. (2013) siRNA targeting Hes5 augments hair cell regeneration in aminoglycoside-damaged mouse utricle. Mol Ther 21:834-41
Shibata, Seiji B; Cortez, Sarah R; Wiler, James A et al. (2012) Hyaluronic acid enhances gene delivery into the cochlea. Hum Gene Ther 23:302-10
Martin, Donna M; Raphael, Yehoash (2012) Have you heard? Viral-mediated gene therapy restores hearing. Neuron 75:188-90
Chikar, Jennifer A; Hendricks, Jeffrey L; Richardson-Burns, Sarah M et al. (2012) The use of a dual PEDOT and RGD-functionalized alginate hydrogel coating to provide sustained drug delivery and improved cochlear implant function. Biomaterials 33:1982-90
Watanabe, Reiko; Morell, Maria H; Miller, Josef M et al. (2012) Nestin-expressing cells in the developing, mature and noise-exposed cochlear epithelium. Mol Cell Neurosci 49:104-9
Shibata, Seiji B; Budenz, Cameron L; Bowling, Sara A et al. (2011) Nerve maintenance and regeneration in the damaged cochlea. Hear Res 281:56-64
Hankenson, F Claire; Wathen, Asheley B; Eaton, Kathryn A et al. (2010) Guinea pig adenovirus infection does not inhibit cochlear transfection with human adenoviral vectors in a model of hearing loss. Comp Med 60:130-5

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