When a HC is killed by noise or aminoglycoside antibiotics, surrounding SCs form a filamentous actin (F-actin) cable that constricts the HC at its apex. Several major stressors cause HC death, 19, 20, 21, 22 including aging, noise trauma, and exposure to therapeutic drugs with ototoxic side effects. 2, 12, 13, 14, 15, 16, 17 Maintaining a fluid barrier at the surface of the sensory epithelium after damage is necessary to preserve the electro-chemical gradient that drives HC depolarization and therefore sensory transduction after the onset of hearing (reviewed in Wangemann). 5, 6, 7, 8, 9, 10, 11 When HCs die, SCs also preserve the integrity and function of the remaining tissue by forming scars and clearing dead HCs. 4 SCs perform many functions, including providing critical trophic factors, preventing excitotoxicity, and mediating regeneration in those systems (non-mammalian vertebrates) capable of replacing lost HCs. 2, 3 HCs are surrounded by glia-like supporting cells (SCs) that are necessary for HC survival and function (reviewed in Monzack et al.). 1 Mechanosensory hair cells (HCs), the receptor cells of hearing and balance, are not regenerated in the adult mammal and their death results in permanent hearing loss. Hearing loss affects more than 360 million people worldwide and is often irreversible. Together, these data point to a broader defect in the ability of the cisplatin-treated SCs, to preserve tissue health in the mature mammalian inner ear. These data are supported by in vivo experiments, in which cochlear SCs show reduced capacity for scar formation in cisplatin-treated mice compared with those treated with aminoglycosides. The surviving SCs constrict fewer HCs and display impaired phagocytosis. In contrast, cisplatin treatment results in accumulation of dead HCs in the sensory epithelium, accompanied by an increase in SC death. SCs then form a phagosome, which can completely engulf the remaining HC body, a phenomenon not previously reported in mammals. Our data indicate that when HCs are killed by aminoglycosides, SCs efficiently remove HC corpses from the sensory epithelium in a process that includes constricting the apical portion of the HC after loss of membrane integrity. Here we have used live confocal imaging of the adult mouse utricle, to examine the SC responses to HC death caused by aminoglycosides or cisplatin. These responses to HC stress and death are critical to the health of the inner ear. Recent data indicate that SCs sense and respond to HC stress, and that their responses can influence HC death, survival, and phagocytosis. Although both classes of drugs are known to kill HCs, their effects on SCs are less well understood. HCs are susceptible to death from aging, noise overexposure, and treatment with therapeutic drugs that have ototoxic side effects these ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic drug cisplatin. Sensory transduction in the inner ear requires both mechanosensory hair cells (HCs) and surrounding glia-like supporting cells (SCs). Hearing loss and balance disorders affect millions of people worldwide.
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