Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid–blood barrier
- 11 June 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (26), 10388-10393
- https://doi.org/10.1073/pnas.1205210109
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 low- and 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.Keywords
This publication has 35 references indexed in Scilit:
- γ-Secretase and Presenilin Mediate Cleavage and Phosphorylation of Vascular Endothelial Growth Factor Receptor-1Published by Elsevier BV ,2011
- Na+/K+-ATPase α1 Identified as an Abundant Protein in the Blood-Labyrinth Barrier That Plays an Essential Role in the Barrier IntegrityPLOS ONE, 2011
- Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differencesFluids and Barriers of the CNS, 2011
- Bone Marrow Cell Recruitment Mediated by Inducible Nitric Oxide Synthase/Stromal Cell-Derived Factor-1α Signaling Repairs the Acoustically Damaged Cochlear Blood-Labyrinth BarrierThe American Journal of Pathology, 2010
- Resident macrophages in the cochlear blood-labyrinth barrier and their renewal via migration of bone-marrow-derived cellsCell and tissue research, 2010
- Pigment epithelium-derived factor inhibits advanced glycation end products-induced retinal vascular permeabilityBiochimie, 2010
- Cochlear Pericyte Responses to Acoustic Trauma and the Involvement of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth FactorThe American Journal of Pathology, 2009
- Protein expression of pigment-epithelium-derived factor in rat cochleaCell and tissue research, 2008
- Connexin30 deficiency causes instrastrial fluid–blood barrier disruption within the cochlear stria vascularisProceedings of the National Academy of Sciences of the United States of America, 2007
- Identification of Two Types of Melanocyte Within the Stria Vascularis of the Mouse Inner EarPigment Cell Research, 1991