Analysis of human perilymph by mass spectrometry and correlation to the patients pathophysiologic changes of inner ear diseases

Introduction:

Diagnostic methods and knowledge about the etiology and pathophysiology of inner ear diseases like enlarged vestibular aqueduct (EVA), otosclerosis, and Ménière's disease (MD), leading to hearing loss and especially to changes of the perilymph composition, are still very limited. This is mainly due to the difficult access to structures and fluids of the inner ear. The aim of the study was to analyze the proteome of human perilymph from cochlear implant patients and to correlate the data with patient's etiology.

Methods:

Human perilymph sampling was performed during cochlear implantation by inserting the tip of a micro glass capillary through the round window membrane. Human perilymph of patients suffering from EVA, otosclerosis and MD were analyzed. Individual proteins were identified by a shot-gun proteomics approach and data-dependent analysis using orbitrap mass spectrometry (Thermo Fisher Scientific) and Max Quant software for identification. Additionally data analysis was performed by Perseus software and Ingenuity Pathway Analysis (IPA).

Results:

By mass spectrometry more than thousand proteins were identified in perilymph samples. Some perilymph proteins show significant differences between the disease groups. The different protein compositions of the three disease groups were deeply analyzed by IPA software for identification of pathways characteristic of patient's etiology. An inflammatory component and an involvement of the complement system in all disease groups was indicated.

Conclusions:

Disease specific biomarkers for the disease groups were defined by IPA software. The role of these proteins in the molecular pathology of EVA, otosclerosis and MD especially the impact in neurology or inflammation remains to be elucidated.

Publication History

Publication Date:
23 April 2019 (online)