Resident Physician University of Kansas Medical Center University of Kansas Medical Center Kansas City, Missouri
Hypothesis: Proteins enriched in the perilymph proteome of Meniere’s disease (MD) patients may implicate cochlear structures and cell types. Utilizing single cell transcriptome datasets from the mammalian cochlea, we hypothesize that these enriched perilymph proteins will localize to specific cochlear cell types.
Background: The limited understanding of human inner ear pathologies and their associated biomolecular variations hinder efforts to develop disease-specific diagnostics and therapeutics. Perilymph sampling and analysis is now furthering characterization of the cochlear microenvironment. Recently, enriched inner ear protein expression has been shown in patients with MD compared to patients with other inner ear diseases. Localizing expression of these proteins to cochlear cell types can further our knowledge of potential disease pathways and subsequent development of targeted therapeutics.
Methods: We compiled previously published data regarding differential perilymph proteome profiles amongst patients with MD, otosclerosis, EVA, SSNHL, and hearing loss of undefined etiology (controls). Enriched proteins in MD were cross-referenced against published single-cell/single-nucleus RNA-seq datasets to localize protein expression to specific cochlear cell types. Datasets included postnatal day 7 and 15 mouse organ of Corti and adult mouse spiral ganglion neurons, Schwann cells, and the stria vascularis.
Results: In silico analysis of single cell transcriptomic datasets localizes enriched perilymph proteins to specific inner ear cell types. We have also identified potential genetic targets within these cochlear regions, which may guide development of future treatment for MD.
Conclusions: Perilymph proteins enriched in MD are expressed by specific cochlear cell types based on in silicolocalization, potentially facilitating development of disease-specific diagnostic markers and therapeutics.
Define Professional Practice Gap & Educational Need: We lack knowledge of molecular processes and their pathologic variations within the inner ear, specifically as this relates to Meniere’s disease (MD). We similarly lack reliable diseasespecific diagnostic markers and therapies. Perilymph analysis has demonstrated multiple potential disease-specific biomarkers, though the cochlear cell type(s) producing these biomolecules remains to be elucidated.
Learning Objective: To appreciate: 1) that differentially enriched perilymph proteins in patients with MD localize to specific cochlear cell types based on in silico data analysis with previously published transcriptome datasets from the innerear; 2) how this data can guide identification of potential genetic/protein targets for diagnosis and treatment of MD.
Desired Result: The audience will better understand perilymph protein expression unique to MD and these various proteins’ localization to specific cells within the cochlea. We also aim for the audience to appreciate how this information can guide discovery of potential disease-specific diagnostics and therapeutics.
Level of Evidence: Level III – Cohort and case-control studies