Effect of Immunophilin Inhibitors on Cochlear Fibroblasts and Spiral Ganglion Cells.
Cell survival
Immunophilin inhibitor
Inner ear
Inner ear therapy
Spiral ganglion neuron
Journal
Audiology & neuro-otology
ISSN: 1421-9700
Titre abrégé: Audiol Neurootol
Pays: Switzerland
ID NLM: 9606930
Informations de publication
Date de publication:
2023
2023
Historique:
received:
24
05
2022
accepted:
02
08
2022
pubmed:
9
9
2022
medline:
20
1
2023
entrez:
8
9
2022
Statut:
ppublish
Résumé
Loss of hair cells and degeneration of spiral ganglion neurons (SGN) lead to severe hearing loss or deafness. The successful use of a cochlear implant (CI) depends among other factors on the number of surviving SGN. Postoperative formation of fibrous tissue around the electrode array causes an increase in electrical impedances at the stimulating contacts. The use of immunophilin inhibitors may reduce the inflammatory processes without suppressing the immune response. Here, we report on in vitro experiments with different concentrations of immunophilin inhibitors MM284 and compound V20 regarding a possible application of these substances in the inner ear. Standard cell lines (NIH/3T3 fibroblasts), freshly isolated SGN, and fibroblasts from neonatal rat cochleae (p3-5) were incubated with different concentrations of immunophilin inhibitors for 48 h. Metabolic activity of fibroblasts was investigated by MTT assay and cell survival by counting of immunochemically stained neurons and compared to controls. MM284 did not affect SGN numbers and neurite growth at concentrations of 4 × 10-5 mol/L and below, whereas V20 had no effect at 8 × 10-6 mol/L and below. Metabolic activity of fibroblasts was unchanged at these concentrations. Especially MM284 might be considered as a possible candidate for application within the cochlea.
Identifiants
pubmed: 36075188
pii: 000526454
doi: 10.1159/000526454
pmc: PMC9909619
doi:
Substances chimiques
Immunophilins
EC 5.2.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
43-51Informations de copyright
© 2022 The Author(s). Published by S. Karger AG, Basel.
Références
J Biol Chem. 2006 May 26;281(21):14961-70
pubmed: 16547004
J Neurocytol. 2002 Sep-Nov;31(8-9):755-63
pubmed: 14501212
Front Neurol. 2020 Apr 15;11:258
pubmed: 32390924
Mol Cell Neurosci. 2006 Apr;31(4):642-8
pubmed: 16446100
Front Neurol. 2022 Apr 15;13:877342
pubmed: 35493807
Laryngorhinootologie. 2014 Sep;93(9):605-11
pubmed: 24936690
Hear Res. 2005 Nov;209(1-2):86-90
pubmed: 16084678
Mol Membr Biol. 2012 May-Jun;29(3-4):107-13
pubmed: 22656651
J Neurosci Res. 2011 Apr;89(4):611-7
pubmed: 21312225
PLoS One. 2018 Mar 27;13(3):e0194778
pubmed: 29584754
PLoS One. 2015 Apr 20;10(4):e0124606
pubmed: 25894208
J Int Med Res. 2009 Sep-Oct;37(5):1528-42
pubmed: 19930861
J Biomed Mater Res A. 2014 Feb;102(2):442-54
pubmed: 23533184
J Biomed Mater Res B Appl Biomater. 2008 Oct;87(1):146-53
pubmed: 18437711
Brain Res. 1979 Oct 5;174(2):283-308
pubmed: 385109
J Neurosci Res. 2004 Nov 1;78(3):383-92
pubmed: 15389832
J Gastroenterol Hepatol. 2011 Mar;26(3):558-67
pubmed: 21332552
Brain Pathol. 2014 Jul;24(4):404-13
pubmed: 24946078
Hear Res. 2001 Sep;159(1-2):125-31
pubmed: 11520640
Front Cell Dev Biol. 2021 Mar 12;9:648461
pubmed: 33777956
Neuroscience. 2009 Jun 16;161(1):227-35
pubmed: 19324078
Neuroreport. 2001 Feb 12;12(2):275-9
pubmed: 11209934
Audiol Neurootol. 2007;12(5):277-84
pubmed: 17536196
PLoS One. 2020 Aug 3;15(8):e0236784
pubmed: 32745116
Int J Mol Sci. 2019 Jan 14;20(2):
pubmed: 30646511
Biochemistry. 2009 Jul 7;48(26):6268-77
pubmed: 19480458
J Med Chem. 1999 Sep 9;42(18):3615-22
pubmed: 10479292
J Biomed Mater Res B Appl Biomater. 2017 May;105(4):715-722
pubmed: 26699416
Int J Pediatr Otorhinolaryngol. 2015 May;79(5):660-5
pubmed: 25746517
Otolaryngol Head Neck Surg. 2009 Aug;141(2):247-52
pubmed: 19643260
Mol Microbiol. 1993 Nov;10(3):445-56
pubmed: 7526121
Neuroscience. 2007 May 11;146(2):833-40
pubmed: 17331652
Hear Res. 2020 May;390:107924
pubmed: 32143111
Neuroreport. 2005 Dec 19;16(18):2011-4
pubmed: 16317344
Cell. 1991 Aug 23;66(4):807-15
pubmed: 1715244
Cell. 1978 May;14(1):43-51
pubmed: 352534
Laryngoscope. 2008 Nov;118(11):2028-35
pubmed: 18818553
PLoS One. 2016 Feb 03;11(2):e0147552
pubmed: 26840740
Cell Mol Life Sci. 2006 Dec;63(24):2889-900
pubmed: 17075696
J Neurosci. 2017 Feb 8;37(6):1413-1427
pubmed: 28011744
Hear Res. 2008 Feb;236(1-2):52-60
pubmed: 18207679
Ann Otol Rhinol Laryngol. 2007 Oct;116(10):731-8
pubmed: 17987778