Defining the Inflammatory Microenvironment in the Human Cochlea by Perilymph Analysis: Toward Liquid Biopsy of the Cochlea

Abstract

The molecular pathomechanisms in the majority of patients suffering from acute or progressive sensorineural hearing loss cannot be determined yet. The size and the complex architecture of the cochlea make biopsy and in-depth histological analyses impossible without severe damage of the organ. Thus, histopathology correlated to inner disease is only possible after death. The establishment of a technique for perilymph sampling during cochlear implantation may enable a liquid biopsy and characterization of the cochlear microenvironment. Inflammatory processes may not only participate in disease onset and progression in the inner ear, but may also control performance of the implant. However, little is known about cytokines and chemokines in the human inner ear as predictive markers for cochlear implant performance. First attempts to use multiplex protein arrays for inflammatory markers were successful for the identification of cytokines, chemokines, and endothelial markers present in the human perilymph. Moreover, unsupervised cluster and principal component analyses were used to group patients by lead cytokines and to correlate certain proteins to clinical data. Endothelial and epithelial factors were detected at higher concentrations than typical pro-inflammatory cytokines such as TNF-a or IL-6. Significant differences in VEGF family members have been observed comparing patients with deafness to patients with residual hearing with significantly reduced VEGF-D levels in patients with deafness. In addition, there is a trend toward higher IGFBP-1 levels in these patients. Hence, endothelial and epithelial factors in combination with cytokines may present robust biomarker candidates and will be investigated in future studies in more detail. Thus, multiplex protein arrays are feasible in very small perilymph samples allowing a qualitative and quantitative analysis of inflammatory markers. More results are required to advance this method for elucidating the development and course of specific inner ear diseases or for perioperative characterization of cochlear implant patients.

Dose-Dependent Transient Decrease of Impedances by Deep Intracochlear Injection of Triamcinolone With a Cochlear Catheter Prior to Cochlear Implantation–1 Year Data

“…In addition, the immunological predisposition of each individual may influence the responsiveness to steroids and other antiinflammatory agents. The initial immunological status before implantation can now be detected in tiny perilymph samples with significant variations between the patients (29). In the future, it may be possible to diagnose just these constellations in which steroid injections are most likely beneficial for the patient.…”

Otoprotection to Implanted Cochlea Exposed to Noise Trauma With Dexamethasone Eluting Electrode

“…It is also interesting to note that in the present study, we observed that ABR thresholds were lower in implanted animals subjected to NT compared to implanted animals or those exposed to NT alone Although the precise reasons for this effect are still not known, it is possible that implanted animals actually receive less sound due to the electrode in the cochlea compared to non-implanted animals. In addition, there is a release of growth factors as well as heat shock proteins (HSP) in the inner ear following CI (Warnecke et al, 2019). Higher insulin-like growth factor binding protein 1 (IGFBP-1) levels have been observed in the perilymph of implanted individuals (Warnecke et al, 2019).…”

“…In addition, there is a release of growth factors as well as heat shock proteins (HSP) in the inner ear following CI (Warnecke et al, 2019). Higher insulin-like growth factor binding protein 1 (IGFBP-1) levels have been observed in the perilymph of implanted individuals (Warnecke et al, 2019). IGFBP1 regulates the action of IGF-1 that plays a crucial role in the embryonic and postnatal development of the cochlea (Camarero et al, 2001; Digicaylioglu et al, 2004; Bach, 2015).…”

Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo

“…A miniaturized variant of the manufacturer's instructions was used. 39 As little as 1-2 μL of the samples was diluted with sample diluent (1:20) and incubated with multiplex beads for 45 minutes, followed by two washings steps. Afterwards, a cocktail of biotinylated secondary murine antibodies was added for 30 minutes and after final washing steps, the streptavidin-PE was added.…”