LAUSR

The fluids of the human inner ear (endolymph and perilymph) are a self-contained system without any direct connection to other body fluids. Therefore, the composition of these fluids is unique. Both fluids differ in their ionic composition, which has to be maintained to ensure auditory and vestibular function within the inner ear. While the ionic concentration of the perilymph is more like that of other extracellular fluids, the composition of the endolymph is comparable to the cytosol [1–3]. Studies on the proteome of the perilymph also showed a high similarity with body fluids like blood plasma and cerebrospinal fluids (CSF) in humans [4, 5]. However, studies concentrating on the miRNA profile of the human endo-/ perilymph are lacking. miRNAs are small, 19–24 nucleotide-long, non-coding RNA fragments that play a major role in the regulation of gene expression in a variety of processes [6]. Differential miRNA expression profiles in blood as well as in CSF have been shown for several diseases, such as acute ischemic stroke or glioblastomas [7, 8]. Extracellular miRNAs are also promising biomarkers in inflammatory and degenerative diseases [9]. In this study, we analyzed a mixture of endoand perilymph (EP) extracted from human temporal bones (postmortem) and serum samples from patients suffering from benign paroxysmal positional vertigo (BPPV) attending the German Center for Vertigo and Balance Disorders in Munich. BPPV patients suffer from a non-autoimmune but rather structural pathologic vertigo, which results from the detachment of otoliths from the utricle, but are generally healthy and thus represent an ideal control group for other inner ear diseases. A total of 12 (5F/7M) EP mixtures (age 56.5 ± 18 years) and 21 (12F/9M) BPPV patients (age 64.8 ± 9 years) were included in this study. The EP mixtures were collected within 24 h post-mortem. Earlier studies have shown that miRNAs are exceptionally stable against degradation or deterioration over a postmortem interval of 4–5 days, thereby reflecting the in vivo situation over a prolonged time [10, 11]. The miRNA profiles were established using the Illumina next-generation sequencing system and were further analyzed using the miRDeep2 and DESeq2 package. We were able to detect a total of 528 different miRNAs in all of our EP samples, whereby the ten most abundant miRNAs represent about 50% of all detected miRNAs. The highest expressed miRNAs within all samples were the miRNAs hsa-miR92a-3p, hsa-miR-320a and hsa-let7b-5p. While miR-92a is known to play a regulatory role during cell cycle and proliferation with tumour-progressive features, the others tend to exert tumour-suppressive and immunomodulatory functions [12–14]. Although the single samples showed a high biological variability, there are only minor, yet significant differences in the miRNA profile of samples from different sexes. Only a single miRNA (hsa-miR-3622a-5p) was significantly expressed differently in women and men with a mean 4.3-fold increase in women (p = 0.033; Benjamini–Hochberg corrected; Fig. 1a). By comparing the EP samples with the serum samples from BPPV patients, we detected a total of 481 differentially expressed miRNAs This manuscript is part of a supplement sponsored by the German Federal Ministry of Education and Research within the funding initiative for integrated research and treatment centers.