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Hair cell loss and repair processes in mammalian vestibular sensory epithelia

Li, Lin; (1997) Hair cell loss and repair processes in mammalian vestibular sensory epithelia. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The sensory hair cells of the inner ear transduce the mechanical stimuli involved in hearing and balance. Loss of hair cells has been thought to be irreversible in mammals and is a major cause of human deafness and vestibular disturbances. In this thesis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), fluorescence microscopy and immunohistochemistry have been used to examine the progression of hair cell loss and subsequent repair processes in the vestibular sensory epithelia of guinea pigs following injury induced by ototoxic aminoglycoside gentamicin. It is found that hair cell recovery may occur in the mammalian vestibular tissues. Hair cell loss in the utricular maculae and cristae was apparent after chronic, systemic gentamicin treatment. With topical application of drug, the saccular macula was also affected. Damaged hair cells undergoing degeneration showed morphological features characteristic of apoptosis. The lost hair cells were replaced by expansion of supporting cells. In longer survival animals, SEM showed there were many cells with immature hair bundles within the areas where hair cells were originally lost. Thin sections of equivalent areas showed the presence of immature hair cells. This suggested that replacement of hair cells occurred spontaneously after gentamicin induced hair cell loss. Studies of this phenomenon over a period of 33 weeks after gentamicin treatment demonstrated that the immature hair cells continued to develop towards structural maturity. The number of hair bundles assessed by SEM of utricles and saccules showed that an initial decrease in number was followed by an increase, confirming recovery of hair cells. However, the hair cell density was lower than in controls, suggesting recovery was still incomplete. A technique for the maintenance of explants of the utricles and saccules from adult guinea pigs and gerbils in organotypic cultures was developed. Exposure of cultures to gentamicin resulted in progressive hair cell loss in a pattern similar to that seen in vivo. The degenerated hair cells again showed morphological features of apoptosis. In situ end labelling (ISEL) method was applied to detect apoptotic cells in the cultured utricles. Immature like hair cells were occasionally identified in cultures exposed to gentamicin. The results suggest that organotypic culture system of the mature mammalian vestibular epithelia is a useful model for examination of ototoxicity and recovery processes. Proliferative activity was identified in the damaged vestibular sensory tissues by immunohistochemical bromodeoxyuridine (BrdU) labelling, but the extent was insufficient to account for the recovery of hair cell numbers. Mechanisms other than proliferation may also be invoked after gentamicin induced hair cell loss in the vestibular sensory epithelia of the mammalian inner ear. Nevertheless, these results show that the potential for replacement of hair cells after loss may exist in the vestibular sensory organs of mature mammals.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Hair cell loss and repair processes in mammalian vestibular sensory epithelia
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10098061
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