TY - JOUR
T1 - Evaluating Neurotrophin Signaling Using MicroRNA Perilymph Profiling in Cochlear Implant Patients with and Without Residual Hearing
AU - Shew, Matthew
AU - Wichova, Helena
AU - Warnecke, Athanasia
AU - Lenarz, Thomas
AU - Staecker, Hinrich
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Hypothesis:MicroRNAs predicted to regulate neurotrophin signaling can be found in human perilymph.Background:Animal and human temporal bone studies suggest that spiral ganglion health can affect cochlear implant (CI) outcomes. Neurotrophins have been identified as a key factor in the maintenance of spiral ganglion health. Changes in miRNAs may regulate neurotrophin signaling and may reflect neurotrophin expression levels.Methods:Perilymph sampling was carried out in 18 patients undergoing cochlear implantation or stapedotomy. Expression of miRNAs in perilymph was evaluated using an Agilent miRNA gene chip. Using ingenuity pathway analysis (IPA) software, miRNAs targeting neurotrophin signaling pathway genes present in a cochlear cDNA library were annotated. Expression levels of miRNAs in perilymph were correlated to the patients' preoperative pure-tone average.Results:Expression of mRNAs coding for neurotrophins and their receptors were identified in tissue obtained from normal human cochlea during skull base surgery. We identified miRNAs predicted to regulate these signaling cascades, including miR-1207-5p, miR-4651, miR-103-3p, miR-100-5p, miR-221-3p, miR-200-3p. There was a correlation between poor preoperative hearing and lower expression of miR-1207 (predicted to regulate NTR3) and miR-4651 (predicted to regulate NTR2). Additionally, miR-3960, miR-4481, and miR-675 showed significant differences in expression level when comparing mild and profound hearing loss patients.Conclusions:Expression of some miRNAs that are predicted to regulate neurotrophin signaling in the perilymph of cochlear implant patients vary with the patient's level of residual hearing. These miRNAs may serve as biomarkers for changes in neurotrophin signaling.
AB - Hypothesis:MicroRNAs predicted to regulate neurotrophin signaling can be found in human perilymph.Background:Animal and human temporal bone studies suggest that spiral ganglion health can affect cochlear implant (CI) outcomes. Neurotrophins have been identified as a key factor in the maintenance of spiral ganglion health. Changes in miRNAs may regulate neurotrophin signaling and may reflect neurotrophin expression levels.Methods:Perilymph sampling was carried out in 18 patients undergoing cochlear implantation or stapedotomy. Expression of miRNAs in perilymph was evaluated using an Agilent miRNA gene chip. Using ingenuity pathway analysis (IPA) software, miRNAs targeting neurotrophin signaling pathway genes present in a cochlear cDNA library were annotated. Expression levels of miRNAs in perilymph were correlated to the patients' preoperative pure-tone average.Results:Expression of mRNAs coding for neurotrophins and their receptors were identified in tissue obtained from normal human cochlea during skull base surgery. We identified miRNAs predicted to regulate these signaling cascades, including miR-1207-5p, miR-4651, miR-103-3p, miR-100-5p, miR-221-3p, miR-200-3p. There was a correlation between poor preoperative hearing and lower expression of miR-1207 (predicted to regulate NTR3) and miR-4651 (predicted to regulate NTR2). Additionally, miR-3960, miR-4481, and miR-675 showed significant differences in expression level when comparing mild and profound hearing loss patients.Conclusions:Expression of some miRNAs that are predicted to regulate neurotrophin signaling in the perilymph of cochlear implant patients vary with the patient's level of residual hearing. These miRNAs may serve as biomarkers for changes in neurotrophin signaling.
KW - Cochlear implantation
KW - Neurotrophin
KW - Perilymph sample
KW - Sensorineural hearing loss
KW - miRNA
UR - http://www.scopus.com/inward/record.url?scp=85114385110&partnerID=8YFLogxK
U2 - 10.1097/MAO.0000000000003182
DO - 10.1097/MAO.0000000000003182
M3 - Article
C2 - 33973949
AN - SCOPUS:85114385110
SN - 1531-7129
VL - 42
SP - E1125-E1133
JO - Otology and Neurotology
JF - Otology and Neurotology
IS - 8
ER -