Download PDF
J Am Acad Audiol 2021; 32(10): 627-635
DOI: 10.1055/s-0041-1742234
Research Article
Special Issue on Hearing Therapeutics and Protective Therapies

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

Helena Wichova
1   House Ear Institute, Los Angeles, California
,
Matthew Shew
2   Department of Otolaryngology Head and Neck Surgery, Washington University School of Medicine in St. Louis, Missouri
,
Jennifer Nelson-Brantley
3   Department of Anatomy and Cell Biology, School of Medicine, University of Kanas, Kansas City, Kansas
,
Athanasia Warnecke
4   Department of Otolaryngology Head and Neck Surgery, Hannover Medical School, Hannover, Germany
,
Sandra Prentiss
5   Department of Otolaryngology Head and Neck Surgery, University of Miami School of Medicine, Miami, Florida
,
Hinrich Staecker
6   Department of Otolaryngology Head and Neck Surgery, University of Kansas School of Medicine, Kansas City Kansas
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

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.

Keywords

perilymph sampling - miRNA - biomarker - cochlear implant outcomes

Disclaimer

Any mention of a product, service, or procedure in the Journal of the American Academy of Audiology does not constitute an endorsement of the product, service, or procedure by the American Academy of Audiology.




Publication History

Received: 22 February 2021

Accepted: 06 December 2021

Article published online:
24 May 2022

© 2022. American Academy of Audiology. This article is published by Thieme.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Landegger LD, Psaltis D, Stankovic KM. Human audiometric thresholds do not predict specific cellular damage in the inner ear. Hear Res 2016; 335: 83-93
    CrossrefPubMedGoogle Scholar
  • 2 Plant K, McDermott H, van Hoesel R, Dawson P, Cowan R. Factors predicting postoperative unilateral and bilateral speech recognition in adult cochlear implant recipients with acoustic hearing. Ear Hear 2016; 37 (02) 153-163
    CrossrefPubMedGoogle Scholar
  • 3 Wilson B. The cochlear implant and possibilities for narrowing the remaining gaps between prosthetic and normal hearing. World J Otorhinolaryngol Neck 2017; 3: 200-210
    CrossrefPubMedGoogle Scholar
  • 4 Wilson BS, Dorman MF. Cochlear implants: a remarkable past and a brilliant future. Hear Res 2008; 242 (1-2): 3-21
    CrossrefPubMedGoogle Scholar
  • 5 Blamey P, Artieres F, Başkent D. et al. Factors affecting auditory performance of postlinguistically deaf adults using cochlear implants: an update with 2251 patients. Audiol Neurotol 2013; 18 (01) 36-47
    CrossrefPubMedGoogle Scholar
  • 6 Carlson ML, Driscoll CLW, Gifford RH, McMenomey SO. Cochlear implantation: current and future device options. Otolaryngol Clin North Am 2012; 45 (01) 221-248
    CrossrefPubMedGoogle Scholar
  • 7 Moberly AC, Bates C, Harris MS, Pisoni DB. The enigma of poor performance by adults with cochlear implants. Otol Neurotol 2016; 37 (10) 1522-1528
    CrossrefPubMedGoogle Scholar
  • 8 Seyyedi M, Viana LM, Nadol Jr JB. Within-subject comparison of word recognition and spiral ganglion cell count in bilateral cochlear implant recipients. Otol Neurotol 2014; 35 (08) 1446-1450
    CrossrefPubMedGoogle Scholar
  • 9 Chevance LG, Galli A, Jeanmaire J. Immuno-electrophoretic study of the human perilymph. Acta Otolaryngol 1960; 52: 41-46
    CrossrefPubMedGoogle Scholar
  • 10 Schmitt HA, Pich A, Schröder A. et al. Proteome analysis of human perilymph using an intraoperative sampling method. J Proteome Res 2017; 16 (05) 1911-1923
    CrossrefPubMedGoogle Scholar
  • 11 Shew M, Warnecke A, Lenarz T, Schmitt H, Gunewardena S, Staecker H. Feasibility of microRNA profiling in human inner ear perilymph. Neuroreport 2018; 29 (11) 894-901
    CrossrefPubMedGoogle Scholar
  • 12 Chadly DM, Best J, Ran C. et al. Developmental profiling of microRNAs in the human embryonic inner ear. PLoS One 2018; 13 (01) e0191452
    CrossrefPubMedGoogle Scholar
  • 13 Burgos K, Malenica I, Metpally R. et al. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology. PLoS One 2014; 9 (05) e94839
    CrossrefPubMedGoogle Scholar
  • 14 Rohde M, Sinicina I, Horn A. et al. MicroRNA profile of human endo-/perilymph. J Neurol 2018; 265 (Suppl. 01) 26-28
    CrossrefPubMedGoogle Scholar
  • 15 Shew M, New J, Wichova H, Koestler DC, Staecker H. Using machine learning to predict sensorineural hearing loss based on perilymph micro RNA expression profile. Sci Rep 2019; 9 (01) 3393
    CrossrefPubMedGoogle Scholar
  • 16 Shew M. et al. MicroRNA profiling as a methodology to diagnose Ménière's disease: potential application of machine learning. Otolaryngol Head Neck Surg 2021; 164 (02) 399-406
    CrossrefPubMedGoogle Scholar
  • 17 Shew M, Wichova H, Warnecke A, Lenarz T, Staecker H. Evaluating neurotrophin signaling using microRNA perilymph profiling in cochlear implant patients with and without residual hearing. Otol Neurotol 2021; 42 (08) e1125-e1133
    CrossrefPubMedGoogle Scholar
  • 18 Irizarry RA, Hobbs B, Collin F. et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003; 4 (02) 249-264
    CrossrefPubMedGoogle Scholar
  • 19 Holden LK, Finley CC, Firszt JB. et al. Factors affecting open-set word recognition in adults with cochlear implants. Ear Hear 2013; 34 (03) 342-360
    CrossrefPubMedGoogle Scholar
  • 20 Holder JT, Dwyer NC, Gifford RH. Duration of processor use per day is significantly correlated with speech recognition abilities in adults with cochlear implants. Otol Neurotol 2020; Feb; 41 (02) e227-e231
    CrossrefPubMedGoogle Scholar
  • 21 Sladen DP, Carlson ML, Dowling BP. et al. Cochlear implantation in adults with asymmetric hearing loss: speech recognition in quiet and in noise, and health related quality of life. Otol Neurotol 2018; 39 (05) 576-581
    CrossrefPubMedGoogle Scholar
  • 22 Hansen MR, Vijapurkar U, Koland JG, Green SH. Reciprocal signaling between spiral ganglion neurons and Schwann cells involves neuregulin and neurotrophins. Hear Res 2001; 161 (1-2): 87-98
    CrossrefPubMedGoogle Scholar
  • 23 Hume CR, Kirkegaard M, Oesterle EC. ErbB expression: the mouse inner ear and maturation of the mitogenic response to heregulin. J Assoc Res Otolaryngol 2003; 4 (03) 422-443
    CrossrefPubMedGoogle Scholar
  • 24 Kanzaki S, Stöver T, Kawamoto K. et al. Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation. J Comp Neurol 2002; 454 (03) 350-360
    CrossrefPubMedGoogle Scholar
  • 25 Leake PA, Rebscher SJ, Dore' C, Akil O. AAV-mediated neurotrophin gene therapy promotes improved survival of cochlear spiral ganglion neurons in neonatally deafened cats: comparison of AAV2-hBDNF and AAV5-hGDNF. J Assoc Res Otolaryngol 2019; 20 (04) 341-361
    CrossrefPubMedGoogle Scholar
  • 26 Watanabe F, Kirkegaard M, Matsumoto S. et al. Signaling through erbB receptors is a critical functional regulator in the mature cochlea. Eur J Neurosci 2010; 32 (05) 717-724
    CrossrefPubMedGoogle Scholar
  • 27 Lu CC, Appler JM, Houseman EA, Goodrich LV. Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly. J Neurosci 2011; 31 (30) 10903-10918
    CrossrefPubMedGoogle Scholar
  • 28 Zhang L, Zhang P, Wang G. et al. Ras and Rap signal bidirectional synaptic plasticity via distinct subcellular microdomains. Neuron 2018; 98 (04) 783-800.e4
    CrossrefPubMedGoogle Scholar
  • 29 Cheng L, Vella LJ, Barnham KJ, McLean C, Masters CL, Hill AF. Small RNA fingerprinting of Alzheimer's disease frontal cortex extracellular vesicles and their comparison with peripheral extracellular vesicles. J Extracell Vesicles 2020; 9 (01) 1766822
    CrossrefPubMedGoogle Scholar
  • 30 Saeedi S, Israel S, Nagy C, Turecki G. The emerging role of exosomes in mental disorders. Transl Psychiatry 2019; 9 (01) 122
    CrossrefPubMedGoogle Scholar
  • 31 Bu H, Wedel S, Cavinato M, Jansen-Dürr P. MicroRNA regulation of oxidative stress-induced cellular senescence. Oxid Med Cell Longev 2017; 2017: 2398696
    PubMedGoogle Scholar
  • 32 Umu SU, Langseth H, Bucher-Johannessen C. et al. A comprehensive profile of circulating RNAs in human serum. RNA Biol 2018; 15 (02) 242-250
    CrossrefPubMedGoogle Scholar
  • 33 Krishnan P, Ghosh S, Wang B. et al. Profiling of small nucleolar RNAs by next generation sequencing: potential new players for breast cancer prognosis. PLoS One 2016; 11 (09) e0162622
    CrossrefPubMedGoogle Scholar
  • 34 Kiss T. Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs. EMBO J 2001; 20 (14) 3617-3622
    CrossrefPubMedGoogle Scholar
  • 35 Huang L, Jiang X, Wang Z, Zhong X, Tai S, Cui Y. Small nucleolar RNA host gene 1: a new biomarker and therapeutic target for cancers. Pathol Res Pract 2018; 214 (09) 1247-1252
    CrossrefPubMedGoogle Scholar
  • 36 Michel CI, Holley CL, Scruggs BS. et al. Small nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic stress. Cell Metab 2011; 14 (01) 33-44
    CrossrefPubMedGoogle Scholar
  • 37 Kishore S, Stamm S. The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C. Science 2006; 311 (5758): 230-232
    CrossrefPubMedGoogle Scholar
  • 38 Balogh E, Chandler JC, Varga M. et al. Pseudouridylation defect due to DKC1 and NOP10 mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis. Proc Natl Acad Sci U S A 2020; 117 (26) 15137-15147
    CrossrefPubMedGoogle Scholar
  • 39 Naiki-Ito A, Naiki T, Kato H. et al. Recruitment of miR-8080 by luteolin inhibits androgen receptor splice variant 7 expression in castration-resistant prostate cancer. Carcinogenesis 2020; 41 (08) 1145-1157
    CrossrefPubMedGoogle Scholar
  • 40 Akers JC, Gonda D, Kim R, Carter BS, Chen CC. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 2013; 113 (01) 1-11
    CrossrefPubMedGoogle Scholar
  • 41 O'Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol 2020; 21 (10) 585-606
    CrossrefPubMedGoogle Scholar
  • 42 Shearer AE, Tejani VD, Brown CJ. et al. In vivo electrocochleography in hybrid cochlear implant users implicates TMPRSS3 in spiral ganglion function. Sci Rep 2018; 8 (01) 14165
    CrossrefPubMedGoogle Scholar
  • 43 Scheperle RA, Abbas PJ. Peripheral and central contributions to cortical responses in cochlear implant users. Ear Hear 2015; 36 (04) 430-440
    CrossrefPubMedGoogle Scholar
  • 44 Green KM, Bhatt Y, Mawman DJ. et al. Predictors of audiological outcome following cochlear implantation in adults. Cochlear Implants Int 2007; 8 (01) 1-11
    CrossrefPubMedGoogle Scholar
  • 45 Carlson ML. Cochlear implantation in adults. N Engl J Med 2020; 382 (16) 1531-1542
    CrossrefPubMedGoogle Scholar
  • 46 Mavel S, Lefèvre A, Bakhos D, Dufour-Rainfray D, Blasco H, Emond P. Validation of metabolomics analysis of human perilymph fluid using liquid chromatography-mass spectroscopy. Hear Res 2018; 367: 129-136
    CrossrefPubMedGoogle Scholar
  • 47 Tong L, Strong MK, Kaur T. et al. Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons. J Neurosci 2015; 35 (20) 7878-7891
    CrossrefPubMedGoogle Scholar
  • 48 Kaur C, Saini S, Pal I. et al. Age-related changes in the number of cresyl-violet-stained, parvalbumin and NMDAR 2B expressing neurons in the human spiral ganglion. Hear Res 2020; 388: 107883
    CrossrefPubMedGoogle Scholar
  • 49 Cremers CWRJ, Delleman WJW. Usher's syndrome, temporal bone pathology. Int J Pediatr Otorhinolaryngol 1988; 16 (01) 23-30
    CrossrefPubMedGoogle Scholar
  • 50 Dabdoub A, Nishimura K. Cochlear implants meet regenerative biology: state of the science and future research directions. Otol Neurotol 2017; 38 (08) e232-e236
    CrossrefPubMedGoogle Scholar
  • 51 Pfingst BE, Colesa DJ, Swiderski DL. et al. Neurotrophin gene therapy in deafened ears with cochlear implants: long-term effects on nerve survival and functional measures. J Assoc Res Otolaryngol 2017; 18 (06) 731-750
    CrossrefPubMedGoogle Scholar
  • 52 Chen W, Jongkamonwiwat N, Abbas L. et al. Restoration of auditory evoked responses by human ES-cell-derived otic progenitors. Nature 2012; 490 (7419): 278-282
    CrossrefPubMedGoogle Scholar
  • 53 O'Connell BP, Holder JT, Dwyer RT. et al. Intra- and postoperative electrocochleography may be predictive of final electrode position and postoperative hearing preservation. Front Neurosci 2017; 11: 291
    CrossrefPubMedGoogle Scholar
  • 54 Schmitt H, Roemer A, Zeilinger C. et al. Heat shock proteins in human perilymph: implications for cochlear implantation. Otol Neurotol 2018; 39 (01) 37-44
    CrossrefPubMedGoogle Scholar