Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763191
Title: The expression of integrins in the human vestibular system
Author: Hussain, Kiran
ISNI:       0000 0004 7660 5540
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Abstract:
The inner ear is responsible for the detection of sound and movement and therefore subserves hearing and balance. The vestibular system is an integral part of the labyrinth that is housed in the otic capsule of the petrous temporal bone. It is made up of five end organs; the three semiHcircular canals, the utricle and saccule. Mechanoreceptive hair cells, supporting cells and nerve endings make up the sensory neuroepithelia of these organs. Loss of the hair cells in the cochlea leads to deafness and loss in the vestibular system causes balance dysfunction, dizziness and vertigo. Unlike in the cochlea, when this loss occurs in the vestibular system there is in fact a limited capacity for regeneration in mammals. Following hair cell loss induced by ototoxic insult, both in vivo and in vitro, some new hair cells can arise spontaneously. In vivo approximately one third of the hair cells might be replaced with spontaneous reHinnervation. The regenerated new hair cells may be due to the direct phenotypic conversion of supporting cell into hair cells without an intervening mitotic event. Integrins are cell adhesion receptors that play important roles in physiological and pathological processes throughout the body including the vestibular system. The 24 αβ heterodimeric members mediate the interaction of cell - cell transmissions as well as cell H extracellular matrix communication. With specific reference to the vestibular system the role of integrins is potentially integral to the repair and recovery process. The lesion created by the death of a hair cell is closed by supporting cells in a manner that maintains the permeability barrier at the luminal surface of the epithelium. This controlled process relies on cell shape changes and spreading that likely involves integrins. Furthermore, the supporting cells remove these dead hair cells by a phagocytic process. Certain integrins are expressed at the surface of cells that recognise apoptotic cells. Their role in the vestibular system in particular has the potential to provide insight into how disorders of this complex system can be better understood and managed. To date this has not been studied in humans. Explant cultures of vestibular tissue is the only means to perform experimental studies upon the viable human ear. The sensory tissues from the human vestibular system can be obtained from patients undergoing trans labyrinthine procedures for acoustic neuromas. Previous work has shown that they can be maintained ex corporeally in explant culture for periods of up to four weeks. This provides a unique opportunity to study this complex system in humans. This study has identified which integrin subunits are present in the human utricle and localised them. The change in their expression and location following ototoxic injury has also been demonstrated. Crucially, α2, α6, α8, αV, β1 and β5 were located to the basement membrane. α6, αV, β1, β3 β5 and β6 all individually demonstrate interesting patterns and have been implicated in previous work, not just limited to within the inner ear, as playing a potential role in the regenerative processes that occur.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.763191  DOI: Not available
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