Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing

Abstract

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice.

Disruption of SorCS2 reveals differences in the regulation of stereociliary bundle formation between hair cell types in the inner ear

“…3 months of age, an increasing number of hair bundles contained very long, thick structures indicating fusion and elongation of stereocilia and fusion of stereocilia with the kinocilium (Fig 10A–10E). Similar fused, elongated stereocilia were present in the maculae of older normal animals (Fig 10F) and have been described in other studies of age-related effects upon macular hair cells [39]. Likewise, stereocilia in the anomalous bundles of cochlear IHC, particularly those in the apical coils, appeared to increase in length with age; by 6 months the height of longer stereocilia in the bundles was ca.…”

Immunohistochemical techniques for the human inner ear

“…Human inner ear tissue (cochlea and vestibular endorgans) obtained from ablative surgery has been useful to investigate the expression of several proteins by IHC, mRNA (Ishiyama et al 2010; Calzada et al 2012b; Liu et al 2015, 2016), and ultrastructural organization of the auditory and vestibular sensory epithelium (Ishiyama et al 2007; McCall et al 2009; Liu et al 2015; Taylor et al 2015). Studies of Cx distribution in the human cochlea: IF and confocal microscopy analysis of Cx proteins in the human cochlea have shown that Cx26 and Cx30 proteins are co-expressed (Liu et al 2009).…”

“…Whole-mount immunostained specimens have also been used to conduct TEM (Nadol et al 1993; McCall et al 2009; Taylor et al 2015). …”

Development and regeneration of vestibular hair cells in mammals

“…Golub et al [133] estimated that 17% of hair cells were replaced in utricles of adult mice. Further, there is morphological evidence that humans, even those who are very old, have the capacity to form new utricular hair cells [137]. This is in stark contrast to the nearby cochlea, in which no hair cells are replaced after damage in adulthood [101] (Fig.…”