A Systematic Review on the Role of the Stria Vascularis in Menière's Disease Pathogenesis

The stria vascularis (SV) is a secretory epithelium that maintains fluid homeostasis and generates the endocochlear potential in the cochlear duct. Multiomic studies have identified genes in the SV that could contribute to the pathogenesis of Menière's Disease (MD), a disorder defined by episodic vertigo, sensorineural hearing loss, and tinnitus. This systematic review identified genes expressed in the SV cell types (marginal, intermediate, and basal) and gap junction proteins to evaluate their pathophysiological connections to MD.

We conducted a literature search on 1293 articles relevant to MD and SV that were screened for SV genes involved in MD. Following quality assessment, 130 studies met the inclusion criteria, comprising 26 human studies, 101 animal studies, and three human-animal studies.

Seven immune-related and six auditory-related genes were identified: CACNA1D, ESRRB, HGF, KCNE1, MDH1, QSOX1, and SLC12A2 (marginal cells); ACTB, TMEM176A, and TMEM176B (intermediate cells); and ACTN1, COL11A2, and GSTM1 (basal cells). Gene-set-enrichment-analysis revealed pathways involving gap-junction assembly and electrical coupling. International Mouse Phenotyping Consortium data showed Gja1 and Kcne1 knockouts have immune system abnormalities. Single-cell RNA sequencing data of the lateral wall revealed high expression of Coch, Dtna, and Prkcb in fibrocytes, Reisner's cells, and immune cells. Furthermore, TWEAK released from intermediate cells and bound to its receptor (TNFRSF12A) in the marginal cells may upregulate NF-κB inflammatory response in MD patients.

We hypothesize that some SV genes may contribute to the audiovestibular phenotype in MD, but most of them play a role in the altered immune response found in Sporadic MD.