Proteome of Human Perilymph

Abstract

Current diagnostic tools limit a clinician’s ability to discriminate between many possible causes of sensorineural hearing loss. This constraint leads to the frequent diagnosis of the idiopathic condition, leaving patients without a clear prognosis and only general treatment options. As a first step toward developing new diagnostic tools and improving patient care, we report the first use of liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to map the proteome of human perilymph. Using LC-MS/MS, we analyzed four samples, two collected from patients with vestibular schwannoma (VS) and two from patients undergoing cochlear implantation (CI). For each cohort, one sample contained pooled specimens collected from five patients and the second contained a specimen obtained from a single patient. Of the 271 proteins identified with high confidence among the samples, 71 proteins were common in every sample, and used to conservatively define the proteome of human perilymph. Comparison to human cerebrospinal fluid and blood plasma, as well as murine perilymph, showed significant similarity in protein content across fluids; however, a quantitative comparison was not possible. Fifteen candidate biomarkers of VS were identified by comparing VS and CI samples. This list will be used in future investigations targeted at discriminating between VS tumors associated with good versus poor hearing.

Quantitative Vestibular Labyrinthine Otopathology in Temporal Bones with Vestibular Schwannoma

“…21 Therefore, it is unlikely that vestibular nerve deafferentation explains our findings. The acidophilic precipitate observed in this study and others, along with increased protein concentrations detected in the perilymph, 15,22 implicates VS-associated abnormalities of inner ear biochemistry. The etiology of increased protein concentrations remains unclear, with theories ranging from alterations in the blood-labyrinth barrier, 22 immune response to tumor antigens, 23 and obstruction of axonal transport of proteins through the compressed or infiltrated eighth nerve.…”

Mechanisms of Hearing Loss in Neurofibromatosis Type 2

“…The importance of elevated intralabyrinthine protein underlying hearing loss is supported by previous studies examining unique perilymphatic proteins that are elevated in CVSs, including μ-Crystallin (CRYM) and low density lipoprotein-related protein 2 (LRP2) [27]. Mutations of these proteins are associated with genetic syndromes that present with deafness not related to tumors.…”

Dysfunction of the Cochlea Contributing to Hearing Loss in Acoustic Neuromas

“…In fact, before the advent of imaging, high protein concentration in a perilymphatic ‘tap’ was used as a diagnostic test to differentiate between hearing loss caused by VS verses Meniere’s syndrome (35,36). More recently, proteomic analysis of inner ear fluids has shown a higher total protein content in VS patients compared to controls (37). …”