Protein expression of pigment-epithelium-derived factor in rat cochlea

Gleich, Otto; Piña, Ana Luisa

doi:10.1007/s00441-008-0608-6

Cited by 4 publications

(6 citation statements)

References 28 publications

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“…Next we examined the mechanism by which PVM/Ms the affect expression of junction proteins. PEDF is a 50-kDa glycoprotein previously found expressed in the rat inner ear, including in the SV (25). In this study, we found that PEDF is expressed in primary cultured PVM/Ms (Fig.…”

Section: Pvms Control Barrier Permeability By Affecting Global Expressupporting

confidence: 62%

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

Zhang

Dai

Fridberger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

201

272

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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. mouse cochlea | paracellular permeability | tight junction | capillary T he intrastrial fluid-blood barrier separates the stria vascularis (SV) from peripheral circulation. The integrity of the barrier is critical for maintaining inner ear homeostasis, especially for sustaining the endocochlear potential (EP), an essential driving force for hearing function (1-4). Disruption of the barrier is closely associated with a number of hearing disorders, including autoimmune inner ear disease, noise-induced hearing loss, agerelated hearing loss, and several genetically linked diseases (5-10). Despite the importance of the intrastrial fluid-blood barrier, little is understood about regulation of the barrier and the mechanisms that control its permeability.In the classic view, the intrastrial fluid-blood barrier comprises basement membrane and endothelial cells (ECs) that connect to each other with tight junctions (11) to form a diffusion barrier that prevents most blood-borne substances from entering the ear (2). In a recent study, we found that the intrastrial fluid-blood barrier also includes a large number of pericytes and perivascular-resident macrophage-like melanocytes (PVM/Ms) (12, 13). The PVM/Ms are not observed in other capillary regions such as in capillary beds of the spiral ligament. The PVM/Ms are in close contact with vessels through cytoplasmic processes. The structural complexity of PVM/Ms' capillar...

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Section: Pvms Control Barrier Permeability By Affecting Global Expressupporting

confidence: 62%

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

Zhang

Dai

Fridberger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

201

272

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“…IHCs, OHCs, and Deiters cells were also PEDF-positive after 120 min. PEDF was not detected in the basilar membrane in guinea pigs, which has been reported in rats (Gleich and Piña, 2008 ). PEDF gene expression was further analyzed using RNAscope in the cochleae of normal guinea pigs and we found mRNA transcripts in spiral ganglion type 1 neurons, type I and type II fibrocytes, marginal cells, and basal cells of the stria vascularis.…”

Section: Discussionmentioning

confidence: 50%

“…It is also reported to have regulating functions in osteogenesis, to promote stem cell renewal and inhibit tumor angiogenesis (Brook et al, 2020 ). PEDF has been identified in the stria vascularis, spiral ganglion, neurons, and basilar membrane in the rat inner ear (Gleich and Piña, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

The Acute Effects of Furosemide on Na-K-Cl Cotransporter-1, Fetuin-A and Pigment Epithelium-Derived Factor in the Guinea Pig Cochlea

Rasmussen

Lundström

Eriksson

et al. 2022

Front. Mol. Neurosci.

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BackgroundFurosemide is a loop diuretic used to treat edema; however, it also targets the Na-K-Cl cotransporter-1 (NKCC1) in the inner ear. In very high doses, furosemide abolishes the endocochlear potential (EP). The aim of the study was to gain a deeper understanding of the temporal course of the acute effects of furosemide in the inner ear, including the protein localization of Fetuin-A and PEDF in guinea pig cochleae.Material and MethodAdult guinea pigs were given an intravenous injection of furosemide in a dose of 100 mg per kg of body weight. The cochleae were studied using immunohistochemistry in controls and at four intervals: 3 min, 30 min, 60 min and 120 min. Also, cochleae of untreated guinea pigs were tested for Fetuin-A and PEDF mRNA using RNAscope® technology.ResultsAt 3 min, NKCC1 staining was abolished in the type II fibrocytes in the spiral ligament, followed by a recovery period of up to 120 min. In the stria vascularis, the lowest staining intensity of NKCC1 presented after 30 min. The spiral ganglion showed a stable staining intensity for the full 120 min. Fetuin-A protein and mRNA were detected in the spiral ganglion type I neurons, inner and outer hair cells, pillar cells, Deiters cells and the stria vascularis. Furosemide induced an increased staining intensity of Fetuin-A at 120 min. PEDF protein and mRNA were found in the spiral ganglia type I neurons, the stria vascularis, and in type I and type II fibrocytes of the spiral ligament. PEDF protein staining intensity was high in the pillar cells in the organ of Corti. Furosemide induced an increased staining intensity of PEDF in type I neurons and pillar cells after 120 min.ConclusionThe results indicate rapid furosemide-induced changes of NKCC1 in the type II fibrocytes. This could be part of the mechanism that causes reduction of the EP within minutes after high dose furosemide injection. Fetuin-A and PEDF are present in many cells of the cochlea and probably increase after furosemide exposure, possibly as an otoprotective response.

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“…Systemic PEDF was shown to improve the EP and hearing thresholds. But PEDF is also found in the organ of Corti (Gleich and Piña, 2008 ) where it may also exert trophic effects. Notably, the mouse strain, age, and type of exposure used in these studies have been shown to produce massive disruption of the organ of Corti (Ohlemiller et al, 2018 ), and strial changes were likely not the major drivers of hearing loss.…”

Section: Strial Barrier Dysfunction Following Noise Exposurementioning

confidence: 99%

A critical evaluation of “leakage” at the cochlear blood-stria-barrier and its functional significance

Ohlemiller,

Dwyer,

Henson

et al. 2024

Front. Mol. Neurosci.

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The blood-labyrinth-barrier (BLB) is a semipermeable boundary between the vasculature and three separate fluid spaces of the inner ear, the perilymph, the endolymph and the intrastrial space. An important component of the BLB is the blood-stria-barrier, which shepherds the passage of ions and metabolites from strial capillaries into the intrastrial space. Some investigators have reported increased “leakage” from these capillaries following certain experimental interventions, or in the presence of inflammation or genetic variants. This leakage is generally thought to be harmful to cochlear function, principally by lowering the endocochlear potential (EP). Here, we examine evidence for this dogma. We find that strial capillaries are not exclusive, and that the asserted detrimental influence of strial capillary leakage is often confounded by hair cell damage or intrinsic dysfunction of the stria. The vast majority of previous reports speculate about the influence of strial vascular barrier function on the EP without directly measuring the EP. We argue that strial capillary leakage is common across conditions and species, and does not significantly impact the EP or hearing thresholds, either on evidentiary or theoretical grounds. Instead, strial capillary endothelial cells and pericytes are dynamic and allow permeability of varying degrees in response to specific conditions. We present observations from mice and demonstrate that the mechanisms of strial capillary transport are heterogeneous and inconsistent among inbred strains.

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Protein expression of pigment-epithelium-derived factor in rat cochlea

Cited by 4 publications

References 28 publications

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

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

The Acute Effects of Furosemide on Na-K-Cl Cotransporter-1, Fetuin-A and Pigment Epithelium-Derived Factor in the Guinea Pig Cochlea

A critical evaluation of “leakage” at the cochlear blood-stria-barrier and its functional significance

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