Abstract
The vast majority of hearing loss, the most common sensory impairment, and vertigo, which commonly causes falls, both reflect underlying dysfunction of inner ear cells. Perilymph sampling can thus provide molecular cues to hearing and balance disorders. While such “liquid biopsy” of the inner ear is not yet in routine clinical practice, previous studies have uncovered alterations in perilymph in patients with certain types of hearing loss. However, the proteome of perilymph from patients with intact hearing has been unknown. Furthermore, no complete characterization of perilymph from patients with vestibular dysfunction has been reported. Here, using liquid-chromatography with tandem mass spectrometry, we analyzed samples of normal perilymph collected from three patients with skull base meningiomas and intact hearing. We identified 228 proteins that were common across the samples, establishing a greatly expanded proteome of the previously inferred normal human perilymph. Further comparison to perilymph obtained from three patients with vestibular dysfunction with drop attacks due to Meniere’s disease showed 38 proteins with significantly differential abundance. The abundance of four protein candidates with previously unknown roles in inner ear biology was validated in murine cochleae by immunohistochemistry and in situ hybridization: AACT, HGFAC, EFEMP1, and TGFBI. Together, these results motivate future work in characterizing the normal human perilymph and identifying biomarkers of inner ear disease.
Highlights
Hearing loss is the most common sensory impairment in humans and it currently disables 466 million people across the globe; this number is expected to rise to 900 million by 2050 [1]
The perilymph proteomes of patients with vestibular dysfunction appeared more heterogeneous and did not cluster along either principal component (Fig 2A). This result indicates that subset of patients with normal hearing and vestibular function shares a signature that distinguishes them from other subsets
We focused on validation of EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) expression in the cochlea because a gene encoding an effector of EGF-mediated cell signaling causes
Summary
Hearing loss is the most common sensory impairment in humans and it currently disables 466 million people across the globe; this number is expected to rise to 900 million by 2050 [1]. Two-thirds of the population aged over 70 in the United states is affected by disabling hearing loss [2]. A vast majority of this burden is due to sensorineural hearing loss (SNHL), which originates from defects in the cochlea, the spiraling organ of the inner ear (Fig 1).
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