Normal Human Middle Ear Research Articles

Surgical reconstruction of the ossicular chain with custom 3D printed ossicular prosthesis

BackgroundConductive hearing loss due to ossicular abnormalities occurs from many causes, including trauma, infection, cholesteatoma, surgery and congenital anomalies. Surgical reconstruction of the ossicular chain is a well-established procedure for repair of ossicular defects, but is still plagued by high failure rates. Underlying disease and proper sizing of prostheses are two challenges that lead to component failure. Three-dimensional (3D) printing has been used successfully to solve a number of medical prosthesis problems. Custom 3D printing an individualized ossicular prosthesis would be a potential solution for the wide range of anatomic variation encountered in the pathological middle ear, and could decrease the rate of post-operative prosthesis displacement by increasing the likelihood of a proper fit, in addition to decreasing surgical time.In this study, the incus was removed from three formalin-fixed cadaveric human temporal bones with no macro- or microscopic evidence of pathology. Imaging of the cadaveric bone was obtained using a standard temporal bone CT protocol. A custom prosthesis for each cadaveric human temporal bone was designed using the Mimics Innovation Suite software (Materialise, Belgium) and fabricated on a Form2 3D printer (FormLabs, Somerville, Massachusetts). Four surgeons then performed insertion of each prosthesis into each middle ear, blinded to the bone from and for which each was designed. The surgeons were asked to match each prosthesis to its correct parent bone.ResultsEach prosthesis had unique measurements. Each of the four surgeons was able to correctly match the prosthesis model to its intended temporal bone. The chances of this occurring randomly are 1:1296.ConclusionsA custom 3D printed ossicular prosthesis is a viable solution for conductive hearing loss due to ossicular chain defects. Commercially available CT scanners can detect significant anatomic differences in normal human middle ear ossicles. These differences can be accurately represented with current 3D printing technology and, more significantly, surgeons can detect these differences.

Expression and Localization of Aquaporin Water Channels in Human Middle Ear Epithelium.

Although aquaporins (AQPs) are known to play critical roles as the basis for water and solute transport in water homeostasis, AQPs in normal human middle ear epithelium (NHMEE) has not previously been investigated. To investigate the expressions of AQP water channels in NHMEE in situ, in proliferating epithelial cell cultures in vitro. AQP 0-12 expressions by cultured NHMEE cells in situ were assessed by reverse transcriptase-polymerase chain reaction. Normal middle ear epithelial tissue was harvested and investigated for expressions of AQPs (1, 3, 4, and 5) by immunohistochemistry. Expression screening was also carried out on the differentiated NHMEE cells. Transcripts for AQP 1, 2, 3, 4, 5, 6, 8, 10, and 11 were expressed consistently in cultured NHMEE cells; however, AQP 0, 7, 9, and 12 subtypes were not expressed. Immunochemistry confirmed the expressions of AQP 1, 3, and 5 at the protein level. AQP 1 was localized at capillary endothelial cells and fibroblasts in lamina propria mucosae; AQP 3 was present solely at the basolateral membrane of ciliated cells, whereas AQP 5 was on the apical surface of ciliated cells. AQP 3 and 5 were intensely expressed in both cultured NHMEE cells in situ and NHMEE tissue in vitro. This is the first study to demonstrate that AQPs are expressed by human middle ear epithelium in situ and in vitro, suggesting a potential role in otitis media with effusion. Our study suggests that the presence of AQP 1, 3, and 5 in the middle ear cavity may be to have an important role for water transportation.

NUMERICAL ANALYSIS OF TYMPANOSCLEROSIS AND TREATMENT EFFECT

Tympanosclerosis is a typical middle ear disease, which is one of the main causes of conduction deafness. We investigate the effects of tympanosclerosis and lesion excision on sound transmission of the human ear by using finite element technique. Based on CT scan images from Zhongshan Hospital of Fudan University on the normal human middle ear, numerical values of the CT scans were obtained by further processing of the images using a self-compiled program. The CT data of the right ear from a healthy volunteer were digitalized and imported into PATRAN software to reconstruct the finite element model of the ear by a self-compiling program. A frequency response analysis was made for the model, and comparative analysis was made between the calculated results and experimental data, which validated the model in this paper. The results show that the sclerosis of the ligaments and tensor muscle in the middle ear caused by force on the ossicles is larger than the normal ear and the amplitude of the stapes footplate is larger than the normal ear. This leads to a decrease of the final conductive hearing function. Furthermore, the excision of the stapes ligament and tensor tympani is good for the restoration of normal hearing. This paper provides new research perspective for clinical treatment.

Uridine-5'-Triphosphate Stimulates Chloride Secretion via Cystic Fibrosis Transmembrane Conductance Regulator and Ca2+-Activated Chloride Channels in Cultured Human Middle Ear Epithelial Cells

Received October 24, 2011 Revised November 6, 2011 Accepted November 14, 2011 Address for correspondence Jae Young Choi, MD, PhD Department of Otorhinolaryngology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Tel +82-2-2228-3600 Fax +82-2-393-0580 E-mail jychoi@yuhs.ac Background and ObjectivesZZNucleotide binding to purinergic P2Y receptors contributes to the regulation of fluid and ion transport in the middle ear epithelial cells. Here, we investigated the regulatory mechanism of the P2Y2 receptor agonist, uridine-5’-triphosphate (UTP), on Cl transport in cultured normal human middle ear epithelial (NHMEE) cells. Materials and MethodZZElectrophysiological measurements were performed in monolayers of cultured NHMEE cells. Short circuit currents (Isc) were measured from the cells mounted in Ussing chambers under various conditions. ResultsZZApical addition of UTP in presence of amiloride evoked a transient rise and a sustained response in Isc due to Cl efflux. Application of different Cl channel blockers to the apical side of the cells significantly decreased UTP-induced Isc. Niflumic acid (NFA), a known blocker of Ca-activated chloride channels (CACC), and CFTRinh172, a selective inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR), partially inhibited the UTP-induced Cl secretion, respectively. ConclusionZZCl transport across the airway epithelia plays a predominant role in regulating airway hydration. In this study, UTP is shown to increase both CACC and CFTR-dependent Cl secretion in NHMEE cells, suggesting their role in fluid and ion transport in the middle ear epithelium. Korean J Otorhinolaryngol-Head Neck Surg 2011;54:840-6

Studies on the mechanics of the normal human middle ear

The middle ear was studied in temporal bone preparations using a laser-Doppler interferometer. For measurements at a sound level of 80 dB SPL this method proved to be very reliable, as was shown by good reproducibility of results in experiments over more than 6 hours. The vibrations of the tympanic membrane and stapes footplate were studied from 200 Hz to 10 KHz and the results demonstrate a piston-like movement of the stapes footplate up to 120 dB SPL. The damping effect of the normal ear is located mainly at the footplate/cochlea level and the middle ear cavity per se does not contribute significantly to the stiffness of the middle ear system.

Activation of epithelial sodium channel in human middle ear epithelial cells by dexamethasone

The middle ear epithelium functions to maintain a fluid-free middle ear cavity. Dysfunction of the middle ear epithelial ion and fluid transport is implicated in the pathogenesis of fluid collection in the middle ear cavity, characteristic of otitis media with effusion. The efficacy of steroid therapy for the treatment of otitis media with effusion remains controversial, and postulated modulation of transepithelial transport function in middle ear epithelia has yet to be demonstrated. The effect of dexamethasone on Na + transport and fluid absorption capacity was investigated in cultured normal human middle ear epithelial (NHMEE) cells. Dexamethasone produced a significant increase in amiloride-sensitive short-circuit current ( Isc). Dexamethasone significantly increased expression levels of mRNAs and proteins of Epithelial Sodium Channel (ENaC)-α and -β subunits. In addition, the ENaC-dependent fluid absorption was significantly increased after dexamethasone treatment. In summary, we have shown that dexamethasone stimulates ENaC activity and ENaC-dependent fluid absorption in NHMEE cells. These findings suggest glucocorticosteroids may be beneficial in treatment of otitis media with effusion by stimulating Na + transport and fluid clearance in the middle ear epithelia.

Interleukin-1β suppresses epithelial sodium channel β-subunit expression and ENaC-dependent fluid absorption in human middle ear epithelial cells

Recent reports have shown that cytokines inhibit fluid absorption by suppressing Na + channel activity in various epithelia. In this study, we investigated the role of epithelial sodium channel (ENaC) in fluid absorption in normal human middle ear epithelial (NHMEE) cells, as well as the effects of Interleukin (IL)-1β on ENaC expression and fluid absorption in NHMEE cells. We confirmed that ENaC α, β and γ were predominantly expressed on the apical surface of the NHMEE cells by immunocytochemistry. Addition of amiloride, a potent ENaC blocker, to apical membranes of NHMEE cells decreased the fluid absorption rate in a dose-dependent manner. Treatment with 10 ng/ml IL-1β for 24 h suppressed ENaC β expression, the ENaC-dependent short-circuit current (Isc), and ENaC-dependent fluid absorption. When the NHMEE cells were pretreated with a phospholipase C (PLC)inhibitor (U73122, 10 μM), a protein kinase C (PKC) inhibitor (Calphostin C, 0.1 μM), or extracellular signal regulated kinase (ERK) 1/2 inhibitor (PD98059, 10 μM), the amiloride-sensitive currents in IL-1β-treated cells were reversed to control levels; an effect not seen with SB202190 (an inhibitor of p38 mitogen-activated protein (MAP) kinase) or SP600125 (a reversible inhibitor of c-Jun N-terminal kinase). In this study we showed that ENaC is essential for fluid absorption in NHMEE cells and that IL-1β suppresses the ENaC-dependent current via the PLC-PKC-ERK1/2 pathway. These results suggest that IL-1β may contribute to fluid retention in otitis media with effusion by changing electrolyte transport and reducing middle ear epithelial fluid absorption.

Interleukin‐1β upregulates Na+‐K+‐2Cl− cotransporter in human middle ear epithelia*

Disruption of periciliary fluid homeostasis is the main pathogenesis of otitis media with effusion (OME), one of the most common childhood diseases. Although the underlying molecular mechanisms are unclear, it has been suggested that the altered functions of ion channels and transporters are involved in the fluid collection of middle ear cavity of OME patients. In the present study, we analyzed the effects of a major cytokine interleukin (IL)-1beta, which was known to be involved in the pathogenesis of OME, on Na(+)-K(+)-2Cl(-) cotransporter (NKCC) in human middle ear cells. Intracellular pH (pH(i)) was measured in primary cultures of normal human middle ear epithelial (NHMEE) cells using a double perfusion chamber, which enabled us to analyze the membrane-specific transporter activities. NKCC activities were estimated by the pH(i) reduction due to bumetanide-sensitive intracellular uptake of NH(4) (+). In NHMEE cells, NKCC activities were observed only in the basolateral membrane, and immunoblotting using specific antibodies revealed the expression of NKCC1. Interestingly, IL-1beta treatments augmented the basolateral NKCC activities and increased NKCC1 expression. In addition, IL-1beta treatments stimulated bumetanide-sensitive fluid transport across the NHMEE cell monolayers. Furthermore, an elevated NKCC1 expression was observed in middle ear cells from OME patients when compared to those from control individuals. The above results provide in vitro and in vivo evidence that the inflammatory cytokine IL-1beta upregulates NKCC1 in middle ear epithelial cells, which would be one of the important underlying mechanisms of excess fluid collection in OME patients.

Dexamethasone increases fluid absorption via Na +/H + exchanger (NHE) 3 activation in normal human middle ear epithelial cells

The proper homeostasis of the liquid lining the surface of the middle ear cavity is vitally important for maintaining a fluid-free middle ear cavity. Disruption of this homeostasis leads to fluid collection in the middle ear cavity and results in otitis media with effusion. We demonstrated the molecular and functional expression of the Na +/H + exchanger (NHE)s in normal human middle ear epithelial (NHMEE) cells. We also evaluated the role of NHEs in fluid absorption and the effect of dexamethasone on NHE function and NHE-dependent fluid absorption in NHMEE cells. Western blot analysis was performed for NHE1, -2, and -3 in NHMEE cells. The fluid absorption rate was measured after liquid application on the luminal surface of the cells. Intracellular pH (pH i) was measured using the pH-sensitive fluorescent probe bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-AM. NHE activity was determined as Na +-induced pHi recovery from an acid load achieved by luminal exposure to 40 mmol/l NH 4Cl. NHE1, -2 and -3 were all expressed in the NHMEE cells. The pH i recovery rate was suppressed by inhibition of NHE2 and -3 with HOE694 at concentrations greater than 50 μM. Inhibition of NHE3 with 650 μM of HOE694 or S3226 significantly decreased the fluid absorption rate. Dexamethasone increased the Na +-induced pH i recovery rate which was reversed by the inhibition of NHE3 with 650 μM of HOE694. Dexamethasone treatment up-regulated NHE3 expression in a dose-dependent manner. The fluid absorption rate was increased by treatment with dexamethasone (10 - 7 M) and reversed by the inhibition of NHE3. In summary, we have shown that NHE3 are involved in the regulation of both pH i and fluid absorption on the luminal surface of NHMEE cells. Dexamethasone stimulates NHE3 expression and NHE3-dependent fluid absorption in NHMEE cells. These findings provide a new insight into mechanisms that regulate periciliary fluid and the therapeutic mechanisms behind steroid treatment of otitis media with effusion.

ENaC- and CFTR-dependent ion and fluid transport in human middle ear epithelial cells

Ion channels, such as the epithelial sodium channel (ENaC), are essential for maintaining a fluid-free middle ear cavity by controlling periciliary fluid. Deviations from the normal volume or compositions of periciliary fluid are probably responsible for otitis media with effusion. To elucidate the physiologic roles of the ENaC and cystic fibrosis transmembrane conductance regulator (CFTR) in the middle ear mucosa, we compared the electrophysiological activity and protein expressions of ENaC and CFTR in normal human middle ear epithelial (NHMEE) cells with those in normal human nasal epithelial (NHNE) cells. We also evaluated the role of ENaC and CFTR in fluid transport by NHMEE cells. Short-circuit current ( I sc) was measured in cell monolayers by modified Ussing chambers. Immunoblotting was performed for ENaC and CFTR. In addition, transepithelial fluid transport was measured after loading 100 μl of fluid onto the luminal cell surface. The amiloride-sensitive Isc in NHMEE cells was much larger than in NHNE cells, whereas the forskolin-induced I sc, presumably mediated by CFTR, was significantly smaller in NHMEE cells. ENaC subunits α, β, and γ were all detected in NHMEE cells, and their expressions were stronger than those in NHNE cells. In comparison, CFTR was also detected in the middle ear mucosa, but at a lower expression level than in NHNE cells. NHMEE cells showed more amiloride-sensitive fluid absorption than NHNE cells. In contrast, fluid absorption was less sensitive to forskolin/IBMX in NHMEE cells than in NHNE cells. The ATP induced Cl − efflux and the amplitude of ATP-induced current in NHMEE cells was much larger than in NHNE cells. In the present study, we have demonstrated an enhanced amiloride-sensitive I sc and fluid absorption in NHMEE cells, where the role of CFTR is limited. Our data also suggest that the ATP-induced Cl − channel could be an alternative Cl − channel to CFTR in NHMEE cells.

P2Y 2 agonist induces mucin secretion via Ca 2+- and inositol 1,4,5-triphosphate-dependent pathway in human middle ear epithelial cells

Purinergic agonists regulate mucin secretion in the airway epithelial cells. This study examined the effects of the apical application of purinergic agonists on Ca 2+ influx ([ Ca 2+] i), and mucin secretion along with their underlying signaling pathway in normal human middle ear epithelial (NHMEE) cells. The apical membrane of NHMEE cells were stimulated with various purinergic agonists, including UTP, and the [ Ca 2+] i was measured using a miniature Ussing double perfusion chamber. P2Y 2 receptor in NHMEE cells was also localized by immunohistochemistry. UTP-induced mucin secretion was quantified by an immunoblotting assay. The order of the purinergic agonist potency with respect to [ Ca 2+] i determined in this study was ATP = UTP > 2-MeSATP > UDP ≫ adenosine which is consistent with that obtained from P2Y 2 receptor activation. The P2Y 2 receptor is expressed in the apical membrane of monolayered cultured NHMEE cells. Apical UTP-induced [ Ca 2+] i was inhibited by 2-aminoethoxydiphenyl borate (2-APB) but not by ryanodine. UTP-induced mucin secretion was inhibited by a Ca 2+ chelating agent, BAPTA-AM, and was stimulated by ionomycin. UTP-induced mucin secretion was also suppressed by U73122 and 2-APB, while Calphostin C suppressed it to a small extent and PD98059 was ineffective. Caffeine also inhibited the UTP-induced [ Ca 2+] i and mucin secretion. These results suggest that the P2Y 2 receptor is expressed in NHMEE cells, and plays a major role in modulating the [ Ca 2+] i from the IP 3-sensitive intracellular Ca 2+ store. UTP-induced mucin secretion in NHMEE cells is strongly dependent on Ca 2+- and IP 3.

IL-1β promotes the ciliogenesis of human middle ear epithelial cells: possible linkage with the expression of mucin gene 8

ConclusionsThese findings suggest that IL-1β increases ciliogenesis in NHMEE cells and that MUC8 protein may play a role in this process. ObjectivesThe morphology of the middle ear epithelium changes under various pathologic conditions. We compared the density of ciliated cells and the level of mucin gene 8 (MUC8) mRNA in the middle ear epithelial cells of mucoid otitis media (MOM) patients with those of normal controls. We also investigated the effect of IL-1β on the ciliogenesis and expression of MUC8 mRNA in cultured normal human middle ear epithelial (NHMEE) cells. In addition, we localized the MUC8 protein in cultured NHMEE cells. Material and methodsThe surface morphology of NHMEE cells was examined using scanning electron microscopy. Reverse transcriptase polymerase chain reaction was performed to determine the level of MUC8 mRNA expression. After synthesis of MUC8 polyclonal antibody, we performed immunohistochemical staining. ResultsThe density of ciliated cells was increased in the middle ear epithelium of both MOM patients and IL-1β-treated cultures. Similarly, the expression of MUC8 was increased in both cases. MUC8 antibody was primarily stained on the ciliated cells of NHMEE cells.

Retinoic Acid Depletion Induces Keratinizing Squamous Differentiation in Human Middle Ear Epithelial Cell Cultures

Objective--The pathogenesis of cholesteatoma behind an intact tympanic membrane remains controversial. Squamous metaplasia of the middle ear mucosa is thought to be a possible mechanism in such cases. However, to date, no definitive experimental results have proved this association. This study was undertaken to investigate whether normal human middle ear epithelial (NHMEE) cells undergo keratinizing squamous differentiation in a retinoic acid (RA)-deficient culture. Material and Methods--We examined the morphological differences between RA-deficient and -sufficient cultures, and determined the expressions of the mucin gene and cornifin-α mRNAs as indicators of mucous and squamous differentiation, respectively. Results--Histomorphologically, the NHMEE cells differentiated into a keratinizing squamous epithelium in RA-deficient cultures. In addition, the expressions of mucin gene 5AC (MUC5AC) and MUC8 mRNAs were suppressed, and the expression of cornifin-α mRNA increased progressively as a function of differentiation in RA-deficient cultures. Conclusions--This study shows that RA depletion induces keratinizing squamous differentiation in NHMEE cell cultures. This finding supports the hypothesis that middle ear cholesteatoma originates from metaplastic middle ear mucosa.

Effect of Uridine 5'-Triphosphate on Mucin and Lysozyme Expression in Human Middle Ear Epithelial Cells

Objective--Extracellular uridine 5′-triphosphate (UTP) regulates a variety of biological functions in the airway epithelium, including chloride and fluid transport, mucociliary clearance and mucin secretion via the P2Y purinergic receptors. This study was undertaken to investigate which P2Y purinergic receptors are expressed in normal human middle ear epithelial (NHMEE) cells. We also determined the levels of mucin and lysozyme secretion and their mRNA expressions following stimulation with UTP in passage-2 cultured NHMEE cells. Material and methods--An immunoblotting assay was performed for quantitation of mucin and lysozyme proteins and RT-PCR for their gene levels after treatment with UTP was done in normal human midle ear epithelial cells. Results--Middle ear epithelial cells expressed P2Y1, P2Y2, P2Y6, P2Y11 and P2Y12 receptors but not P2Y4 receptor. Apically applied UTP induced increased mucin and lysozyme secretion, as measured by dot blotting. In contrast, UTP did not enhance mucin and lysozyme mRNA expression until 72 h after treatment. Conclusion--This study suggests that UTP acts as a secretogogue on mucin and lysozyme secretion in NHMEE cells via the P2Y2 and/or P2Y6 receptor.

Ciliary and Secretory Differentiation of Normal Human Middle Ear Epithelial Cells

Recent technical advances now permit the serial culture of normal human middle ear epithelial (NHMEE) cells. However, the ciliary differentiation of these cells has not been achieved. The purpose of this study was to establish a culture system in order to differentiate serially cultured NHMEE cells into ciliated cells. If ciliated cells developed, the percentages of ciliated cells and secretory cells were measured throughout the duration of culture. We also examined the levels of mucin and lysozyme secretion and their mRNAs in a time-dependent manner. Human middle ear mucosa with a normal appearance was harvested and serially cultured after enzymatic disaggregation. These cells were cultured in an air-liquid interface (ALI) culture system for 2, 7, 14, 21 and 28 days after confluence. Ciliogenesis usually began 16-18 days after confluence. The percentage of ciliated cells detected by means of immunohistochemical staining increased over time up to a maximum of 10.6% but the percentage of secretory cells remained stable at 40% throughout the duration of culture. By Day 14 after confluence, the amounts of mucin and lysozyme secretion, as measured by dot-blotting analysis, had increased significantly and then remained stable. The expression levels of mucin gene 5B ( MUC5B ), MUC8 and lysozyme increased with the duration of culture. MUC8 in particular showed a dramatic increase on Day 28 after confluence. In contrast, the level of MUC5AC mRNA peaked on Day 14 after confluence, and then decreased. In conclusion, ciliary differentiation of NHMEE cells can be induced using an ALI culture system. Our study also suggests that secretory function develops earlier than ciliogenesis, and that the expressions of MUC5B and MUC8 mRNAs increase as a function of differentiation.

Carbon dioxide exchange via the mucosa in healthy middle ear.

Recent studies have shown that gas exchange via the middle ear mucosa, which is performed between the middle ear cleft and capillaries in the submucosal connective tissue, has an essential role in ventilation and pressure regulation in the middle ear cleft. We speculated that gas exchange via the mucosa is induced by the gas diffusion caused by the partial pressure gradient of gas between the middle ear cleft and submucosal capillaries. To evaluate the capacity of the gas exchange via the mucosa in the healthy middle ear of humans by examining the effect of the respiratory mode on middle ear pressure. We selected 13 volunteers ranging in age from 25 to 44 years with healthy ear drums and type A tympanograms. Middle ear pressure was measured in 1 ear of each subject every 2 minutes using tympanometry while the respiratory mode was altered, with the subject in the supine position. The partial pressure of carbon dioxide in the venous blood (PvCO2) and middle ear pressure were decreased by hyperventilation and increased by hypoventilation. The partial pressure of oxygen in the venous blood showed little change. Carbon dioxide diffused into the blood from the middle ear cleft in accord with the partial pressure gradient when the PvCO2 was reduced by hyperventilation, resulting in a decrease of middle ear pressure, whereas CO2 diffused into the middle ear cleft when the PvCO2 was elevated by hypoventilation, resulting in an increase of middle ear pressure. These findings suggest that a bidirectional CO2 exchange via the middle ear mucosa functions in the normal human middle ear.

Studies on the mechanics of the normal human middle ear.

The middle ear was studied in temporal bone preparations using a laser-Doppler interferometer. For measurements at a sound level of 80 dB SPL this method proved to be very reliable, as was shown by good reproducibility of results in experiments over more than 6 hours. The vibrations of the tympanic membrane and stapes footplate were studied from 200 Hz to 10 KHz and the results demonstrate a piston-like movement of the stapes footplate up to 120 dB SPL. The damping effect of the normal ear is located mainly at the footplate/cochlea level and the middle ear cavity per se does not contribute significantly to the stiffness of the middle ear system.

Gamma-carboxyglutamate in normal and pathological human middle ear bones.

The presence of the amino acid gamma-carboxyglutamate (GLA) was established in human middle ear bones. Proteins containing GLA have been described as being associated with normal as well as pathological calcifications. The GLA content of human incus, malleus, and stapes with 1-2 nmol/mg bone is in the range previously reported for a variety of bone. A limited number of samples with middle ear pathology, including otosclerosis, did not show altered GLA levels.

The Fine Surface View of the Normal Human Adult Middle Ear Mucosa

The Fine Surface View of the Normal Human Adult Middle Ear Mucosa

Distribution and density of goblet cells in the normal adult human middle ear.

The purpose of this study was to map the distribution and density of goblet cells in the clinically normal middle ear. From 12 temporal bones, derived from 12 adult patients with clinically normal middle ears, the mucosa was prepared and stained by the PAS-alcian blue whole-mount method. In six of the patients the middle ears with meticulous gross and microscopic investigation showed mild sequelae of previous otitis media, called the slightly abnormal series, whereas the other six patients who had entirely normal middle ears were designated the normal series. Each middle ear was investigated in 12 different areas: tympanic orifice, hypotympanum anteriorly and posteriorly, round window niche, oval window niche, promontory anteriorly, in the middle, and posteriorly, epitympanum, antrum, and mastoid process. In each middle ear area the goblet-cell density and distribution were determined on the basis of 30 to 50 counts of 0.01768 mm2 epithelial surface, a total of at least 4800 counts. In six patients goblet cells were found in all 12 areas, in three patients in 11, and in three patients in 10. In both series there was a distinct decrease in goblet-cell density from the tympanic orifice, towards the posterior areas of the middle ear and the mastoid process. However, two patients of the slightly abnormal series exhibited a considerably greater density in the posterior than in the anterior part of the hypotympanum. The mean goblet-cell density in the slightly abnormal series was distinctly greater in all middle ear areas than in the normal series. Correspondingly, goblet cells were demonstrated in the antrum and mastoid process in all patients of the slightly abnormal series, but in only half of the normal series. Therefore, the greater goblet-cell density in the slightly abnormal series presumaby results from a previous past disease condition of the middle ear.