Emerging Mechanisms in the Pathogenesis of Menière's Disease: Evidence for the Involvement of Ion Homeostatic or Blood-Labyrinthine Barrier Dysfunction in Human Temporal Bones.
Journal
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
ISSN: 1537-4505
Titre abrégé: Otol Neurotol
Pays: United States
ID NLM: 100961504
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
medline:
10
11
2023
pubmed:
21
9
2023
entrez:
21
9
2023
Statut:
ppublish
Résumé
Analysis of human temporal bone specimens of patients with Menière's disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens. MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear. Understanding these changes may facilitate the identification of more targeted therapies for MD. Human temporal bones from patients with MD (n = 8) and age-matched control patients (n = 8) were processed with immunohistochemistry stains to detect known protein expression related to ionic homeostasis and barrier function in the cochlea, including CLDN11, CLU, KCNJ10, and SLC12A2. Immunofluorescence intensity analysis was performed to quantify protein expression in the stria vascularis, organ of Corti, and spiral ganglion neuron (SGN). Expression of KCNJ10 was significantly reduced in all cochlear regions, including the stria vascularis (9.23 vs 17.52, p = 0.011), OC (14.93 vs 29.16, p = 0.014), and SGN (7.69 vs 18.85, p = 0.0048) in human temporal bone specimens from patients with MD compared with control, respectively. CLDN11 (7.40 vs 10.88, p = 0.049) and CLU (7.80 vs 17.51, p = 0.0051) expression was significantly reduced in the SGN. The results of this study support that there may be differences in the expression of proteins related to ionic homeostasis and barrier function within the cochlea, potentially supporting the role of targeted therapies to treat MD.
Sections du résumé
HYPOTHESIS
OBJECTIVE
Analysis of human temporal bone specimens of patients with Menière's disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens.
BACKGROUND
BACKGROUND
MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear. Understanding these changes may facilitate the identification of more targeted therapies for MD.
METHODS
METHODS
Human temporal bones from patients with MD (n = 8) and age-matched control patients (n = 8) were processed with immunohistochemistry stains to detect known protein expression related to ionic homeostasis and barrier function in the cochlea, including CLDN11, CLU, KCNJ10, and SLC12A2. Immunofluorescence intensity analysis was performed to quantify protein expression in the stria vascularis, organ of Corti, and spiral ganglion neuron (SGN).
RESULTS
RESULTS
Expression of KCNJ10 was significantly reduced in all cochlear regions, including the stria vascularis (9.23 vs 17.52, p = 0.011), OC (14.93 vs 29.16, p = 0.014), and SGN (7.69 vs 18.85, p = 0.0048) in human temporal bone specimens from patients with MD compared with control, respectively. CLDN11 (7.40 vs 10.88, p = 0.049) and CLU (7.80 vs 17.51, p = 0.0051) expression was significantly reduced in the SGN.
CONCLUSION
CONCLUSIONS
The results of this study support that there may be differences in the expression of proteins related to ionic homeostasis and barrier function within the cochlea, potentially supporting the role of targeted therapies to treat MD.
Identifiants
pubmed: 37733989
doi: 10.1097/MAO.0000000000004016
pii: 00129492-990000000-00407
doi:
Substances chimiques
SLC12A2 protein, human
0
Solute Carrier Family 12, Member 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1057-1065Informations de copyright
Copyright © 2023, Otology & Neurotology, Inc.
Déclaration de conflit d'intérêts
Conflicts of Interest: The authors disclose no conflicts of interest.
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