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Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid–blood barrier
Open accessAbstract
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.
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“A human marker for low eumelanin (light eye color) and sunlight sensitivity of skin correlate with reduced inner ear melanin, greater temporary hearing loss after loud sounds, and noise-induced deafness (188, 184, 189, 190).”
From Chemiexcitation: Mammalian Photochemistry in the Dark† (2023) · cites this paper as [188]
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Metadata
- Authors
- Zhang, W., Dai, M., Fridberger, A., Hassan, A., DeGagne, J., Neng, L., Zhang, F., He, W., Ren, T., Trune, D., Auer, M., & Shi, X.
- Affiliations
- Oregon Health & Science University (US)
- Karolinska Institutet (SE)
- Lawrence Berkeley National Laboratory (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-06-11
- Volume
- 109
- Issue
- 26
- Pages
- 10388-10393
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3387119
- OpenAlex
- W1988390197
- Cited by
- 236
- References
- 35
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 22 · 2023: 24 · 2022: 22 · 2021: 20 · 2020: 21 · 2019: 16 · 2018: 13 · 2017: 24 · 2016: 7 · 2015: 14 · 2014: 12 · 2013: 6 · 2012: 2
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel National Institute for Health Policy Research
- National Institutes of Health (DC005983)
- National Institute on Deafness and Other Communication Disorders (R01DC004554, NIH P30 DC005983, DC005983, R01DC010844, R03DC008888, DC008888-02A1, P30DC005983, DC 008888-02S1)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Keywords
- inner ear, stria vascularis, pigment epithelium-derived factor, tight junctions, endocochlear potential, hearing loss, cochlea, pericytes, basement membrane
- MeSH terms
- Animals, Humans, Ear, Inner, Macrophages, Melanocytes, Mice, Transgenic, Stria Vascularis, Tight Junctions, Mice
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