Circulating Clues in Ménière’s Disease: Elevated Cell-Free DNA and a Pro-Inflammatory Signature in Patients’ Blood

Ménière’s disease (MD) is thought to involve dysfunction of the blood–labyrinth barrier, but circulating mechanisms of endothelial injury remain poorly understood. The present study investigated whether cell-free DNA (cfDNA) and inflammatory mediators in plasma contribute to vascular stress and barrier disruption in MD. cfDNA levels were significantly elevated in plasma from patients compared with plasma from healthy controls. Exposure of primary human stria vascularis endothelial cell monolayers to plasma from MD patients led to decreased transepithelial electrical resistance and a significant increase in FITC-dextran permeability, indicating impaired barrier function. MD plasma also induced higher lactate dehydrogenase release and pronounced F-actin disorganization with reduced syndecan-1 expression, consistent with endothelial cytotoxicity and glycocalyx degradation. DNase I partially reversed these effects, implicating extracellular DNA as a key driver. Furthermore, IL-1β, CCL3 (MIP-1α), and CCL27 were elevated in MD plasma. Collectively, our data support a model in which cfDNA and inflammatory mediators cooperatively induce endothelial injury, cytoskeletal remodeling, and glycocalyx shedding, leading to blood–labyrinth barrier weakening. Targeting extracellular DNA or glycocalyx preservation may represent a novel strategy to protect inner ear vascular integrity and modify disease progression in MD, and cfDNA-related readouts may be promising biomarkers of endothelial damage.