microRNAs in sudden hearing loss

Nunez, Desmond A.; Wijesinghe, Printha; Nabi, Shahin; Yeh, David H.; Garnis, Cathie

doi:10.1002/lary.28327

Cited by 22 publications

(40 citation statements)

References 39 publications

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“…We can only interrogate and infer mRNA regulation, and we do not directly identify genes involved with Menière's disease ( 24 ). Despite this limitation, we know miRNAs play a key mechanistic role in various inner ear pathologies such as sudden hearing loss and inner ear development ( 26 , 27 , 29 , 30 ). Additionally, miRNAs have been identified within all main cellular compartments, exosomes, and cell free components throughout the body and have been successfully used as biomarkers for other neurodegenerative diseases like Alzheimer's and Parkinson's ( 25 , 36 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

“…In order to further understand miRNA interactions within the human inner ear, we used IPA software to predict potential interactions with genes expressed in a normal hearing human cochlea (GEO Series accession number GSE128505 ) ( 10 , 29 ). Secondly, in order to identify miRNAs that are clinically relevant, we screened the identified miRNA-mRNA interactions for genes that have been identified to play a pathologic role in Meniere's disease in either animal models or population studies ( 30 – 33 ). Key miRNAs identified were then compared the miRNA expression levels in the serum of patients with Meniere's disease and controls.…”

Section: Methodsmentioning

confidence: 99%

“…miRNA molecules are conserved throughout multiple species, have been identified in tissue and fluids throughout the body, and are known to play a significant role in various pathologies including cancer and other neurodegenerative diseases ( 25 , 26 ). miRNAs have also been shown to play a key role in inner ear development and show distinct expression patterns in patients with hearing loss compared to healthy controls, making them an intriguing biomarker ( 27 – 30 ). In previous work, we preliminary established Meniere's disease could be diagnosed based on perilymph miRNA profile alone, further validating miRNAs as a potential biomarker either through the perilymph or serum of patients ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

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Distinct MicroRNA Profiles in the Perilymph and Serum of Patients With Menière's Disease

et al. 2021

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Hypothesis: Menière's disease microRNA (miRNA) profiles are unique and are reflected in the perilymph and serum of patients.Background: Development of effective biomarkers for Menière's disease are needed. miRNAs are small RNA sequences that downregulate mRNA translation and play a significant role in a variety of disease states, ultimately making them a promising biomarker. miRNAs can be readily isolated from human inner ear perilymph and serum, and may exhibit disease-specific profiles.Methods: Perilymph sampling was performed in 10 patients undergoing surgery; 5 patients with Meniere's disease and 5 patients with otosclerosis serving as controls. miRNAs were isolated from the serum of 5 patients with bilateral Menière's disease and compared to 5 healthy age-matched controls. For evaluation of miRNAs an Agilent miRNA gene chip was used. Analysis of miRNA expression was carried out using Qlucore and Ingenuitey Pathway Analysis software. Promising miRNAs biomarkers were validated using qPCR.Results: In the perilymph of patients with Menière's disease, we identified 16 differentially expressed miRNAs that are predicted to regulate over 220 different cochlear genes. Six miRNAs are postulated to regulate aquaporin expression and twelve miRNAs are postulated to regulate a variety of inflammatory and autoimmune pathways. When comparing perilymph with serum samples, miRNA-1299 and−1270 were differentially expressed in both the perilymph and serum of Ménière's patients compared to controls. Further analysis using qPCR confirmed miRNA-1299 is downregulated over 3-fold in Meniere's disease serum samples compared to controls.Conclusions: Patients with Ménière's disease exhibit distinct miRNA expression profiles within both the perilymph and serum. The altered perilymph miRNAs identified can be linked to postulated Ménière's disease pathways and may serve as biomarkers. miRNA-1299 was validated to be downregulated in both the serum and perilymph of Menière's patients.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Distinct MicroRNA Profiles in the Perilymph and Serum of Patients With Menière's Disease

et al. 2021

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“…Recent studies have shown the potential of developing biomarkers for hearing loss with serum analysis of proteins and miRNAs. 19 There is a need for a “liquid biopsy” or an equivalent to evaluate the inner ear in a patient-specific fashion. Perilymph profiling may offer a solution.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Profiling as a Methodology to Diagnose Ménière’s Disease: Potential Application of Machine Learning

Shew

Wichova

Bur

et al. 2020

Otolaryngol.--head neck surg.

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Objective Diagnosis and treatment of Ménière’s disease remains a significant challenge because of our inability to understand what is occurring on a molecular level. MicroRNA (miRNA) perilymph profiling is a safe methodology and may serve as a “liquid biopsy” equivalent. We used machine learning (ML) to evaluate miRNA expression profiles of various inner ear pathologies to predict diagnosis of Ménière’s disease. Study Design Prospective cohort study. Setting Tertiary academic hospital. Subjects and Methods Perilymph was collected during labyrinthectomy (Ménière’s disease, n = 5), stapedotomy (otosclerosis, n = 5), and cochlear implantation (sensorineural hearing loss [SNHL], n = 9). miRNA was isolated and analyzed with the Affymetrix miRNA 4.0 array. Various ML classification models were evaluated with an 80/20 train/test split and cross-validation. Permutation feature importance was performed to understand miRNAs that were critical to the classification models. Results In terms of miRNA profiles for conductive hearing loss versus Ménière’s, 4 models were able to differentiate and identify the 2 disease classes with 100% accuracy. The top-performing models used the same miRNAs in their decision classification model but with different weighted values. All candidate models for SNHL versus Ménière’s performed significantly worse, with the best models achieving 66% accuracy. Ménière’s models showed unique features distinct from SNHL. Conclusions We can use ML to build Ménière’s-specific prediction models using miRNA profile alone. However, ML models were less accurate in predicting SNHL from Ménière’s, likely from overlap of miRNA biomarkers. The power of this technique is that it identifies biomarkers without knowledge of the pathophysiology, potentially leading to identification of novel biomarkers and diagnostic tests.

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“…Inner ear specific proteins have been found in the serum of animal models of ototoxicity and in human vestibular disease (Liba et al, 2017;Mulry & Parham, 2019;Parham et al, 2019). Serum miRNA associated with sudden sensorineural hearing loss have also been found in humans (Li et al, 2017;Nunez, Wijesinghe, Nabi, Yeh, & Garnis, 2020). It is presently not known either of these is associated with exosomes that have been transported out of the inner ear.…”

Section: Discussionmentioning

confidence: 99%

Isolation of sensory hair cell specific exosomes in human perilymph

Zhuang

Phung

Warnecke

et al. 2021

Preprint

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Evaluation of hearing loss patients using clinical audiometry has been unable to give a definitive cellular or molecular diagnosis, hampering the development of treatments of sensorineural hearing loss. However, biopsy of inner ear tissue without losing residual hearing function for pathologic diagnosis is extremely challenging. In a clinical setting, perilymph can be accessed, so alternative methods for molecular characterization of the inner ear may be developed. Recent approaches to improving inner ear diagnostics have been focusing on the evaluation of the proteomic or miRNA profiles of perilymph. Inspired by recent characterization and classification of many neurodegenerative diseases using exosomes which not only are produced in locally in diseased tissue but are transported beyond the blood brain barrier, we demonstrate the isolation of human inner ear specific exosomes using a novel ultrasensitive immunomagnetic nano pom-poms capture-release approach. Using perilymph samples harvested from surgical procedures, we were able to isolate exosomes from sensorineural hearing loss patients in only 2-5 micro liter of perilymph. By isolating sensory hair cell derived exosomes through their expression level of myosin VII, we for the first time sample material from hair cells in the living human inner ear. This work sets up the first demonstration of immunomagnetic capture-release nano pom-pom isolated exosomes for liquid biopsy diagnosis of sensorineural hearing loss. With the ability to isolate exosomes derived from different cell types for molecular characterization, this method also can be developed for analyzing exosomal biomarkers from more accessible patient tissue fluids such as plasma.

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microRNAs in sudden hearing loss

Cited by 22 publications

References 39 publications

Distinct MicroRNA Profiles in the Perilymph and Serum of Patients With Menière's Disease

Distinct MicroRNA Profiles in the Perilymph and Serum of Patients With Menière's Disease

MicroRNA Profiling as a Methodology to Diagnose Ménière’s Disease: Potential Application of Machine Learning

Isolation of sensory hair cell specific exosomes in human perilymph

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