Mechanisms of Sensory Hair Cell Survival and Death

National Institute On Deafness And Other Communication Disorders

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Abstract

Research in the Section on Sensory Cell Biology is focused on mechanosensory hair cells, which are the receptor cells of hearing and balance. Sensory hair cells transduce sound energy or head movement into neural input to the brain. Hair cells are sensitive to death from a variety of stresses, including noise trauma, aging, certain genetic mutations, and exposure to therapeutic drugs with ototoxic side effects. While hair cell death is followed by robust regeneration that restores hearing and balance function in non-mammalian vertebrates, the capacity for hair cell regeneration is extremely limited in the mature mammalian inner ear. Thus hair cell death in mammals results in permanent hearing loss and/or balance disturbances. Our basic science studies are designed to examine the mechanisms that underlie sensory hair cell death and survival. Our translational studies are designed to use this mechanistic knowledge to guide the rational design of therapies aimed at preventing or reversing hearing loss in humans. Two major questions are currently being studied in the Section on Sensory Cell Biology: 1. What are the cellular and molecular signals that determine whether a hair cell under stress lives or dies? 2. How can we translate these survival vs. death signals into clinical therapies to prevent hearing loss? In the first group of studies, we recently showed that glia-like supporting cells that surround sensory hair cells are the major phagocytic cells that remove dead/dying hair cells from the sensory epithelium (Monzack et al., 2015 Cell Death Differ.). In addition we have shown that these supporting cells secrete HSP70 in a stress-induced response that protects hair cells against death caused by exposure to ototoxic drugs. These data indicate that supporting cells are critical determinants of the fate of a stressed or damaged sensory hair cell. In addition, we have recently shown that resident macrophages in the ear can also reduce hair cell death in an HSP-dependent manner (Baker et al., 2015 J. Assoc. Res. Otolaryngol). Our studies aimed at developing clinical therapies to reduce hearing loss currently include 1) preclinical studies aimed at optimizing sound therapy to reduce cisplatin-induced hearing loss, and 2) studies aimed at determining if FDA-approved drugs reduce cisplatin-induced hearing loss in animal models.