Defective α-tectorin may involve tectorial membrane in familial Meniere disease.
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SUBMITTER: Roman-Naranjo P
PROVIDER: S-EPMC9162437 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
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Defective α-tectorin may involve tectorial membrane in familial Meniere disease.
Roman-Naranjo Pablo P Parra-Perez Alberto M AM Escalera-Balsera Alba A Soto-Varela Andres A Gallego-Martinez Alvaro A Aran Ismael I Perez-Fernandez Nicolas N Bächinger David D Eckhard Andreas H AH Gonzalez-Aguado Rocio R Frejo Lidia L Lopez-Escamez Jose A JA
Clinical and translational medicine 20220601 6
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Project description:The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear sensory epithelium and plays an essential role in auditory transduction. The TM forms facing the luminal endolymph-filled space and exhibits complex ultrastructure. Contrary to the current extracellular assembly model, which posits that secreted collagen fibrils and ECM components self-arrange in the extracellular space, we show that surface tethering of α-tectorin (TECTA) via a glycosylphosphatidylinositol anchor is essential to prevent diffusion of secreted TM components. In the absence of surface-tethered TECTA, collagen fibrils aggregate randomly and fail to recruit TM glycoproteins. Conversely, conversion of TECTA into a transmembrane form results in a layer of collagens on the epithelial surface that fails to form a multilayered structure. We propose a three-dimensional printing model for TM morphogenesis: A new layer of ECM is printed on the cell surface concomitant with the release of a preestablished layer to generate the multilayered TM.
| S-EPMC6881170 | biostudies-literature
Project description:The tectorial membrane (TM) is an apical extracellular matrix (ECM) in the cochlea essential for auditory transduction. The TM exhibits highly ordered domain-specific architecture. Alpha-tectorin/TECTA is a glycosylphosphatidylinositol (GPI)-anchored ECM protein essential for TM organization. Here, we identified that TECTA is released by distinct modes: proteolytic shedding by TMPRSS2 and GPI-anchor-dependent release from the microvillus tip. In the medial/limbal domain, proteolytically shed TECTA forms dense fibers. In the lateral/body domain produced by the supporting cells displaying dense microvilli, the proteolytic shedding restricts TECTA to the microvillus tip and compartmentalizes the collagen-binding site. The tip-localized TECTA, in turn, is released in a GPI-anchor-dependent manner to form collagen-crosslinking fibers, required for maintaining the spacing and parallel organization of collagen fibrils. Overall, we showed that distinct release modes of TECTA determine the domain-specific organization pattern, and the microvillus coordinates the release modes along its membrane to organize the higher-order ECM architecture.
| S-EPMC10802356 | biostudies-literature
Project description:Meniere disease (MD) is a rare disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. The phenotype is variable, and it may be associated with other comorbidities such as migraine, respiratory allergies, and several autoimmune disorders. The condition has a significant heritability according to epidemiological and familial segregation studies. Familial MD is found in 10% of cases, the most frequently found genes being OTOG, MYO7A, and TECTA, previously associated with autosomal dominant and recessive non-syndromic SNHL. These findings suggest a new hypothesis where proteins involved in the extracellular structures in the apical surface of sensory epithelia (otolithic and tectorial membranes) and proteins in the stereocilia links would be key elements in the pathophysiology of MD. The ionic homeostasis of the otolithic and tectorial membranes could be critical to suppress the innate motility of individual hair cell bundles. Initially, focal detachment of these extracellular membranes may cause random depolarization of hair cells and will explain changes in tinnitus loudness or trigger vertigo attacks in early stages of MD. With the progression of the disease, a larger detachment will lead to an otolithic membrane herniation into the horizontal semicircular canal with dissociation in caloric and head impulse responses. Familial MD shows different types of inheritance, including autosomal dominant and compound recessive patterns and implementation of genetic testing will improve our understanding of the genetic structure of MD.
| S-EPMC10335989 | biostudies-literature
Project description:The tectorial membrane is an extracellular structure of the cochlea. It develops on the surface of the auditory epithelium and contains collagen fibrils embedded in a tectorin-based matrix. The collagen fibrils are oriented radially with an apically directed slant - a feature considered crucial for hearing. To determine how this pattern is generated, collagen-fibril formation was examined in mice lacking a tectorin-based matrix, epithelial cilia or the planar cell polarity genes Vangl2 and Ptk7 In wild-type mice, collagen-fibril bundles appear within a tectorin-based matrix at E15.5 and, as fibril number rapidly increases, become co-aligned and correctly oriented. Epithelial width measurements and data from Kif3acKO mice suggest, respectively, that radial stretch and cilia play little, if any, role in determining normal collagen-fibril orientation; however, evidence from tectorin-knockout mice indicates that confinement is important. PRICKLE2 distribution reveals the planar cell polarity axis in the underlying epithelium is organised along the length of the cochlea and, in mice in which this polarity is disrupted, the apically directed collagen offset is no longer observed. These results highlight the importance of the tectorin-based matrix and epithelial signals for precise collagen organisation in the tectorial membrane.
| S-EPMC5702074 | biostudies-literature
Project description:Familial Meniere Disease (FMD) is a rare inner ear disorder characterized by episodic vertigo associated with sensorineural hearing loss, tinnitus and/or aural fullness. We conducted a systematic review to find sequencing studies segregating rare variants in FMD to obtain evidence to support candidate genes for MD. After evaluating the quality of the retrieved records, eight studies were selected to carry out a quantitative synthesis. These articles described 20 single nucleotide variants (SNVs) in 11 genes (FAM136A, DTNA, PRKCB, COCH, DPT, SEMA3D, STRC, HMX2, TMEM55B, OTOG and LSAMP), most of them in singular families-the exception being the OTOG gene. Furthermore, we analyzed the pathogenicity of each SNV and compared its allelic frequency with reference datasets to evaluate its role in the pathogenesis of FMD. By retrieving gene expression data in these genes from different databases, we could classify them according to their gene expression in neural or inner ear tissues. Finally, we evaluated the pattern of inheritance to conclude which genes show an autosomal dominant (AD) or autosomal recessive (AR) inheritance in FMD.
| S-EPMC7761472 | biostudies-literature
Project description:Meniere Disease (MD) is an idiopathic inner ear disease with complex etiology and pathogenesis, which is still unclear. With the development in gene analysis technology, the genetic research of MD has attracted extensive attention, resulting in a large number of studies on the research of the relationship between human genes and MD. This paper aims to review the studies on this topic in recent years. The studies mainly focused on the genetics of familial MD and the correlation between MD and potentially related functional genes. The results of these studies have demonstrated the complexity and diversity of the pathogenesis of MD with both genetic and epigenetic alterations, suggesting that MD might be related to inflammation, immunity, aqua and ion balance in the lymphatic fluid, virus infection, metabolism, and abnormal function of nerve conduction. The finding of rare mutations in TECTA, MYO7A and OTOG genes and other genes such as CDH23, PCDH15 and ADGRV1 in the same families suggest that the integrity of the stereocilia and their interaction with the tectorial and otolithic membranes could be involved in the pathophysiology of familial MD.
| S-EPMC10011279 | biostudies-literature
Project description:Introduction The nature and extent of membrane damage encountered in Meniere disease remains unexplained. Pressure-induced membrane stress may underlie the characteristic hydropic distention. Analysis of stress in the several vestibular chambers may offer insight into the nature and progression of Meniere disease. Objective Membrane stress levels will be assessed by constructing a specific model of the human membranous labyrinth through the application of human dimensions to an existing generic model of the mammalian labyrinth. Methods Nominal dimensions for a model of the human membranous labyrinth were obtained from fixed human tissue. Stress proclivities were calculated and normalized based on shell theory applied to the various geometric figures comprising the model. Results Normalized peak stress levels were projected to be highest in the saccule (38.8), followed by the utricle (5.4), then ampulla (2.4), and lowest in the canal system (1.0). These results reflect macrostructural variations in membrane shape, size, and thickness among the several chambers of the labyrinth. These decreasing stress proclivities parallel the decreasing frequency of histologic lesions found in documented cases of Meniere disease. Conclusions This model analysis of a human membranous labyrinth indicates that substantial disparities in stress exist among the several vestibular chambers due to macrostructural membrane configuration. Low stress levels in the canals are the result of thick highly curved membranes, and the high levels computed for the saccule reflect its thin and relatively flat membranes. These findings suggest that chamber configuration may be a factor controlling the progression of endolymphatic hydrops in Meniere disease.
| S-EPMC4593924 | biostudies-other
Project description:Microscale mechanical probes were designed and bulk-fabricated for applying shearing forces to biological tissues. These probes were used to measure shear impedance of the tectorial membrane (TM) in two dimensions. Forces were applied in the radial and longitudinal directions at frequencies ranging from 0.01-9 kHz and amplitudes from 0.02-4 microN. The force applied was determined by measuring the deflection of the probes' cantilever arms. TM impedance in the radial direction had a magnitude of 63 +/- 28 mN x s/m at 10 Hz and fell with frequency by 16 +/- 0.4 dB/decade, with a constant phase of -72 +/- 6 degrees . In the longitudinal direction, impedance was 36 +/- 9 mN x s/m at 10 Hz and fell by 19 +/- 0.4 dB/decade, with a constant phase of -78 +/- 4 degrees . Impedance was nearly constant as a function of force except at the highest forces, for which it fell slightly. These results show that the viscoelastic properties of the TM extend over a significant range of audio frequencies, consistent with a poroelastic interpretation of TM mechanics. The shear modulus G' determined from these measurements was 17-50 kPa, which is larger than in species with a lower auditory frequency range. This value suggests that hair bundles cannot globally shear the TM, but most likely cause bulk TM motion.
| S-EPMC2517030 | biostudies-literature
Project description:Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evidence to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.
| S-EPMC8901949 | biostudies-literature
Project description:ImportanceA connection between Meniere disease (MD) and migraine has been proposed, but the temporal association remains unknown.ObjectiveTo examine the bidirectional association of MD with migraine.Design, setting, and participantsThis case-control study included participants 40 years or older from the Korean National Health Insurance Service Health Screening Cohort from 2002 to 2015.Main outcomes and measuresA total of 6919 patients with MD were matched with 27 676 control participants without MD for age, sex, income, region of residence, and index date. The incidence of migraine was analyzed in the MD and matched groups using a stratified Cox proportional hazard regression model. In addition, 35 889 patients with migraine were matched with 71 778 control participants without migraine. The incidence of MD was analyzed using a stratified Cox proportional hazard regression model.ResultsOf 142 262 total participants, 94 611 (66.5%) were women. Migraine occurred in 695 of 6919 patients with MD (10.0%) and 970 of 27 676 matched control participants (3.5%). The MD group demonstrated a 2.22-fold higher risk of migraine than the matched control group (95% CI, 1.99-2.49). Meniere disease was present in 1098 of 35 889 patients with migraine (3.1%) and 781 of 71 778 matched control participants (1.1%). The migraine group had a 1.95-fold higher risk of MD than the matched control group (95% CI, 1.77-2.15).Conclusions and relevanceThe results of this case-control study suggest that patients with MD had a greater risk of migraine occurrence. Furthermore, patients with migraine had a higher risk of MD. Based on the bidirectional association, therapeutics for migraine could potentially be applied to MD and vice versa.
| S-EPMC8990355 | biostudies-literature