MicroRNA profile of human endo-/perilymph

Rohde, Markus; Sinicina, Inga; Horn, Anja K. E.; Eichner, Norbert; Meister, Gunter; Strupp, Michael; Himmelein, Susanne

doi:10.1007/s00415-018-8862-3

Cited by 4 publications

(5 citation statements)

References 15 publications

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“…Furthermore, inhalation of hydrogen gas was protective from ROS-mediated NIHL, and metabolic changes associated with hydrogen gas administration were reflected in perilymph [26]. Changes in cytokines such as tumor necrosis factor and interleukin 6 have also been detected after noise exposure using perilymph sampling in mice [20]. Although not currently relevant for understanding human disease, these findings suggest that profiling of ROS species and cytokines in human perilymph may lead to a further understanding of the mechanisms of NIHL as well as other subtypes of SNHL that may involve the ROS or inflammatory pathway.…”

Section: Noise-induced Hearing Lossmentioning

confidence: 98%

“…More recently, postmortem analysis of perilymph has been used to catalog the presence of miRNA in the cochlea. For example, over 500 miRNAs have been detected in the endolymph and perilymph of postmortem samples, with 481 differentially expressed in patients with a vestibular disorder called benign paroxysmal positional vertigo [20].…”

Section: Postmortem Profilingmentioning

confidence: 99%

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A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics

Peter

Warnecke

Staecker

2022

JCM

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In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate between subtypes. This often leaves patients with generalized treatment options such as steroids, hearing aids, or cochlear implantation. The gold standard for localizing disease is direct biopsy or imaging of the affected tissue; however, the inaccessibility and fragility of the cochlea make these techniques difficult. Thus, the establishment of an indirect biopsy, a sampling of inner fluids, is needed to advance inner ear diagnostics and allow for the development of novel therapeutics for inner ear disease. A promising source is perilymph, an inner ear liquid that bathes multiple structures critical to sound transduction. Intraoperative perilymph sampling via the round window membrane of the cochlea has been successfully used to profile the proteome, metabolome, and transcriptome of the inner ear and is a potential source of biomarker discovery. Despite its potential to provide insight into inner ear pathologies, human perilymph sampling continues to be controversial and is currently performed only in conjunction with a planned procedure where the inner ear is opened. Here, we review the safety of procedures in which the inner ear is opened, highlight studies where perilymph analysis has advanced our knowledge of inner ear diseases, and finally propose that perilymph sampling could be done as a stand-alone procedure, thereby advancing our ability to accurately classify sensorineural hearing loss.

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Section: Noise-induced Hearing Lossmentioning

confidence: 98%

Section: Postmortem Profilingmentioning

confidence: 99%

A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics

Peter

Warnecke

Staecker

2022

JCM

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“…One report summarized the miRNA profile in human inner ear fluid to be distinct from the profile found in serum. 6 Although miR-219a-5p has been demonstrated to regulate VC, 4 the underlying mechanism remains unknown. In the present study, we explored the regulatory effect of miR-219a-5p in VC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐219a‐5p−mediated inhibition of CaMKIIγ facilitates vestibular compensation in acute vertigo by promoting protein kinase C expression

Huang

2020

Annals of the New York Academy of Sciences

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Vestibular compensation (VC) refers to a behavioral recovery process in which firing rates of bilateral vestibular nuclei neurons are rebalanced. Our study aimed to investigate the underlying mechanism by which miR‐219a‐5p regulates Ca2+/calmodulin–dependent protein kinase II γ isoform (CaMKIIγ) and protein kinase C (PKC) in VC. A unilateral vestibular deafferentation rat model was established by unilateral labyrinthectomy (UL), after which VC was evaluated in rats with UL‐induced vertigo‐like behavior by measuring vestibular defect behavior and performing rotarod tests, as well as by BrdU immunohistochemistry on medial vestibular nuclei. We found that miR‐219a‐5p was increased while CaMKIIγ was decreased during VC in the medial vestibular nucleus of rats that had undergone UL. Next, gain‐ and loss‐of‐function assays were conducted to evaluate the effects of miR‐219a‐5p and CaMKIIγ on the vestibular defect behaviors and VC, the results of which suggested that in rats after UL overexpression of CaMKIIγ inhibited VC, while overexpression of miR‐219a‐5p facilitated VC. A dual‐luciferase reporter gene assay identified that miR‐219a‐5p targeted CaMKIIγ. This led to additional experiments showing that miR‐219a‐5p aptomir expression downregulated CaMKIIγ in cortical cells with a concomitant increase in PKC expression, which were verified further in vivo. In summary, in rats with acute vertigo, miR‐219a‐5p overexpression inhibits CaMKIIγ and elevates PKC, thereby facilitating VC. Our study offers possible targets for further evaluation as treatment of acute vertigo in humans.

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mentioning

confidence: 99%

“…13 Within the human inner ear, miRNAs have been characterized in post-mortem specimens using previously fixed slides of cochleae, and in intraoperatively collected perilymph samples. 12,14,15 The goal of the present study was to identify perilymph miRNA fingerprints that may serve as potential biomarkers for prediction of post implantation outcomes. Perilymph was sampled in a series of adults undergoing CI via the round window approach.…”

mentioning

confidence: 99%

MicroRNA Profiling in the Perilymph of Cochlear Implant Patients: Identifying Markers that Correlate to Audiological Outcomes

et al. 2021

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Hypothesis MicroRNA (miRNA) expression profiles from human perilymph correlate to post cochlear implantation (CI) hearing outcomes. Background The high inter-individual variability in speech perception among cochlear implant recipients is still poorly understood. MiRNA expression in perilymph can be used to characterize the molecular processes underlying inner ear disease and to predict performance with a cochlear implant. Methods Perilymph collected during CI from 17 patients was analyzed using microarrays. MiRNAs were identified and multivariable analysis using consonant-nucleus-consonant testing at 6 and 18 months post implant activation was performed. Variables analyzed included age, gender, preoperative pure tone average (PTA), and preoperative speech discrimination (word recognition [WR]). Gene ontology analysis was performed to identify potential functional implications of changes in the identified miRNAs. Results Distinct miRNA profiles correlated to preoperative PTA and WR. Patients classified as poor performers showed downregulation of six miRNAs that potentially regulate pathways related to neuronal function and cell survival. Conclusion Individual miRNA profiles can be identified in microvolumes of perilymph. Distinct non-coding RNA expression profiles correlate to preoperative hearing and postoperative cochlear implant outcomes.

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MicroRNA profile of human endo-/perilymph

Cited by 4 publications

References 15 publications

A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics

A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics

MicroRNA‐219a‐5p−mediated inhibition of CaMKIIγ facilitates vestibular compensation in acute vertigo by promoting protein kinase C expression

MicroRNA Profiling in the Perilymph of Cochlear Implant Patients: Identifying Markers that Correlate to Audiological Outcomes

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