Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid-blood barrier

Wenjing Zhang, Min Dai, Anders Fridberger, Ahmed Hassan, Jacqueline DeGagne, Lingling Neng, Fei Zhang, Wenxuan He, Tianying Ren, Dennis Trune, Manfred Auer, Xiaorui Shi

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

The microenvironment of the cochlea is maintained by the barrier between the systemic circulation and the fluids inside the stria vascularis. However, the mechanisms that control the permeability of the intrastrial fluid-blood barrier remain largely unknown. The barrier comprises endothelial cells connected to each other by tight junctions and an underlying basement membrane. In a recent study, we found that the intrastrial fluid-blood barrier also includes a large number of perivascular cells with both macrophage and melanocyte characteristics. The perivascular-resident macrophage-like melanocytes (PVM/Ms) are in close contact with vessels through cytoplasmic processes. Here we demonstrate that PVM/Ms have an important role in maintaining the integrity of the intrastrial fluid-blood barrier and hearing function. Using a cell culture-based in vitro model and a genetically induced PVM/M-depleted animal model, we show that absence of PVM/Ms increases the permeability of the intrastrial fluid-blood barrier to both lowand high-molecular-weight tracers. The increased permeability is caused by decreased expression of pigment epithelial-derived factor, which regulates expression of several tight junction-associated proteins instrumental to barrier integrity. When tested for endocochlear potential and auditory brainstem response, PVM/M-depleted animals show substantial drop in endocochlear potential with accompanying hearing loss. Our results demonstrate a critical role for PVM/Ms in regulating the permeability of the intrastrial fluid-blood barrier for establishing a normal endocochlear potential hearing threshold.

Original languageEnglish (US)
Pages (from-to)10388-10393
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number26
DOIs
StatePublished - Jun 26 2012

Keywords

  • Capillary
  • Mouse cochlea
  • Paracellular permeability
  • Tight junction

ASJC Scopus subject areas

  • General

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