Changes in the inner ear structures in cystic fibrosis patients

Abstract

Objective Although prolonged use of antibiotics is very common in cystic fibrosis (CF) patients, no studies have assessed the changes in both cochlear and peripheral vestibular systems in this population. Methods We used human temporal bones to analyze the density of vestibular dark, transitional, and hair cells in specimens from CF patients who were exposed to several types of antibiotics, as compared with specimens from an age-matched control group with no history of ear disease or antibiotic use. Additionally, we analyzed the changes in the elements of the cochlea (hair cells, spiral ganglion neurons, and the area of the stria vascularis). Data was gathered using differential interference contrast microscopy and light microscopy. Results In the CF group, 83% of patients were exposed to some ototoxic drugs, such as aminoglycosides. As compared with the control group, the density of both type I and type II vestibular hair cells was significantly lower in all structures analyzed; the number of dark cells was significantly lower in the lateral and posterior semicircular canals. We noted a trend toward a lower number of both inner and outer cochlear hair cells at all turns of the cochlea. The number of spiral ganglion neurons in Rosenthal’s canal at the apical turn of the cochlea was significantly lower; furthermore, the area of the stria vascularis at the apical turn of the cochlea was significantly smaller. Conclusions Deterioration of cochlear and vestibular structures in CF patients might be related to their exposure to ototoxic antibiotics. Well-designed case-control studies are necessary to rule out the effect of CF itself.

A Novel Mouse Model of Aminoglycoside-Induced Hyperacusis and Tinnitus

“…Although we did not observe significant synapse degradation/loss, we did observe changes in ABR wave III/I ratios indicating physiological changes between the peripheral and central auditory system (Dehmel et al, 2012;Gu et al, 2012;Lowe and Walton, 2015), which may be explained by "synaptopathy/hidden hearing loss, " or damage to the peripheral afferent system in the absence of significant hair cell loss (Schaette and McAlpine, 2011;Kujawa and Liberman, 2015). Growing evidence suggests that SGNs or their synapses are preferentially targeted by AGs (Liu et al, 2013;Hong et al, 2018) which has also been shown to be true in histological analysis from human cadavers (Sone et al, 1998;Pauna et al, 2017). Importantly, mechanistic understandings of the peripheral and central issues related to AG treatment should be elucidated further.…”

“…Animal models have demonstrated varying degrees of AG-induced cochlear hair cell damage and subsequent hearing loss ( Huth et al, 2011 ; Ogier et al, 2020 ). However, emerging evidence suggests that SGNs, and their specialized ribbon synapses may also be damaged by AGs ( Sone et al, 1998 ; Pauna et al, 2017 ; Hong et al, 2018 ). Such peripheral pathology evidenced in models of noise-induced and age-related hearing loss ( Kujawa and Liberman, 2015 ), has been shown to contribute to central maladaptive plasticity ( Gold and Bajo, 2014 ; Eggermont, 2017 ).…”

Tobramycin and vestibulotoxicity: retrospective analysis of four cases

“… 5 Further research is needed to define the possible characteristics that underlie this toxicity. Pauna et al 8 found histopathological changes due to exposure to aminoglycosides in the vestibular structures of human temporal bone specimens from deceased donors with CF. However, one can speculate that the vestibular structures are intrinsically changed in patients with CF.…”

Functional interplay between CFTR and pendrin: physiological and pathophysiological relevance

“…A hypothesis of a functional interplay between CFTR and pendrin in the stria vascularis is tempting and would require the precise identification of the cell types expressing CFTR. Various degrees of hearing loss and alteration of the inner ear structures, including atrophy of the stria vascularis, have been described in CF patients [118]. Although these derangements have been linked to the use of ototoxic antibiotics, it has been suggested that exposure to aminoglycosides is not the only causal factor for hearing loss in CF [119].…”