Fig. 9.1
(a) The schema showing the morphological relationship between the organ of Corti and TM. The limbal zone is the lesion where TM is attached to the spiral limbus, and the middle zone stretches over the internal sulcus and the organ of Corti, including inner hair cells (IHC) and outer hair cells (OHC). The marginal zone consists the outer edge of TM. The descriptions on the right show the components of TM. (b) Domain structures of the three non-collagenous glycoproteins of the TM. Red = vWF type D repeat, purple = vWF type B repeat, green = ZP domain, C = cysteine knot, TSP = threonine/serine/proline-rich region, ENT = nidogen/entactin G1 domain, black = hydrophobic N-terminal signal peptide (right) or hydrophobic C-termini (left), yellow = region lacking any significant homology to other proteins
The morphology of the cochlear duct in birds is different from that in mammals [4]. The auditory sensory epithelium besides TM is called the basilar papilla, which is the long plain band containing multiple rows of hair cells. The tall narrow hair cells (THC) are located on the neural edge of the continuum, and the short wide hair cells (SHC) on its abneural edge.
9.2 Composition
TM is a gelatinous structure, 97 % of which is composed of water. About 50 % of the dry weight is formed by genetically determined collagens of type II, V, IX, and XI. The remaining components include proteoglycans (25 %) and non-collagenous glycoproteins (25 %), namely α-tectorin (Tecta), β-tectorin (Tectb), and otogelin [5]. Tecta, Tectb, and otogelin are specifically highly expressed in the inner ear. Tecta and Tectb form the striated sheet matrix, where they help organize the collagen fibers.
The cDNA sequence of Tecta contains an entactin G1-like domain at the N-terminal, five elements of von Willebrand factor (vWF) type D repeats, and a zona pellucida (ZP) domain at the C-terminal. Tecta protein is divided into three regions connected to each other via disulfide bonds. The cDNA sequence of Tectb is shorter than that of Tecta, containing a single ZP domain. The ZP domain is known to help in the formation of homopolymers and heteropolymers [6]. The sequence of otogelin contains several vWF type D repeats, a threonine/serine/proline-rich region, five elements of vWF type B repeats, and a C-terminal cysteine knot.
The central core of TM is composed of bundles of 20-nm collagen filaments that are embedded in an unusual striated sheet matrix [7]. This striated sheet matrix is composed of two types of thin filaments (7–9 nm), the light staining type and the dark staining type, coupled by staggered cross-bridges [7]. The upper surface of TM is covered by the covernet, a large network of anastomosing caliber fibrils.
9.3 Function
The mechanical role of TM in hearing is not fully recognized. In fact, it has been disregarded in previous cochlear models. More recent models, however, suggest the improvement of hearing sensitivity by strong TM radial coupling to outer hair cell bundles [8]. Frequency sensitivity was also shown to be improved by weak TM longitudinal coupling to outer hair cells [9]. These observations are supported by data obtained in transgenic mice [10–12], as described in the next paragraph.
9.4 Phenotype of Knockout Mice
Tecta ΔENT/ΔENT mice, which have the homozygous in-frame deletion of entactin G1 section of Tecta, lack almost all non-collagenous matrixes of TM. As a consequence, TM is almost completely detached from the organ of Corti and the surface of the spiral limbus [13]. Tecta ΔENT/ΔENT mice display moderate hearing loss of about 60–80 dB at 20 kHz and less severe hearing impairment at higher frequencies.
Mice with heterozygous mutation of Tecta Y1870C (the missense mutation detected in an Australian family with moderate to severe hearing impairment of about 60–80 dB) show an unusual TM of humpbacked shape with decreased attachment area, dilated space under TM, and loss of striated sheet matrix at the sulcus region [14]. Tecta Y1870C/+ mice, however, demonstrated normal function of outer hair cells and BM motion. The compound action potential threshold of Tecta Y1870C/+ mice was on average 55 dB higher than that of the Tecta +/+ mouse, suggesting the essential role of TM in driving inner hair cells relating to motion of outer hair cell bundles.
Mice with homozygous mutation of the functional null deletion of Tectb gene have TM attached to the spiral limbus and the surface of the organ of Corti [15]. The knockout mice lack the organized striated sheet matrix which is characteristic in the wild-type mice. Instead, collagen fibrils are embedded in the matrix and dispersed randomly, and the abnormal filaments are formed by Tecta. The knockout mice of Tectb display severe hearing impairment at frequencies of 20 kHz or less, which is probably caused by the enlargement and bulging of TM at the apex of the cochlea.
Otogelin knockout mice have TM attached to the epithelia of the cochlea and almost normal microstructure with the atypical rodlike shape in the limbal zone [16]. The knockout mice have severe balance disorder and various degrees of hearing impairment. The mechanism underlying hearing dysfunction has not been elucidated yet.
Mice with homozygous mutations of the Col11a2 and Col9a1 genes, which form the collagen fibers inside TM, also have hearing impairment [17–19]. These mice lack the organization of the collagen fibrils, but it is difficult to evaluate the specific influence of the mutation in TM function, because Col11a2 and Col9a1 are broadly expressed in the multiple structures of the ear.
9.5 Known Mutation Causing Hearing Defects in Humans
A Tecta mutation associated with hearing impairment has been identified in a total of 15 families worldwide [20]. However, phenotypic differences of patients bearing Tecta mutations revealed the possible involvement of different genotypes [21]. All loss-of-function mutations of Tecta support its recessive heredity and cause stable, moderate to severe hearing loss from prelingual stage. All the missense mutations of Tecta involving cysteine residues are autosomal dominant and result in progressive hearing loss [22]. The pathogenesis may be the disruption of disulfide bonds and the resultant instability of the matrix structures. Missense mutations involving amino acids other than cysteine cause stable hearing loss.
9.6 Clinical Implications
Linthicum et al. compared the temporal bone pathologies of patients with idiopathic sudden sensory hearing loss (ISSNHL) with those of known vascular impairment due to surgical interventions [23]. Histological analysis of tissues from ISSNHL patients more frequently revealed abnormal TM morphology, such as the separation of TM from the organ of Corti, than the postoperative vascular group. These findings draw attention to the unrecognized vulnerability of TM to inflammatory processes, which might result in sensory neural hearing loss.
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