Distribution of Immune Cells Including Macrophages in the Human Cochlea

Background: The human cochlea was earlier believed to lack capacity to mount specific immune responses. Recent studies established that the human cochlea holds macrophages. The cells appear to surveil, dispose of, and restore wasted cells to maintain tissue integrity. Macrophage activities are believed to be the central elements in immune responses and could swiftly defuse invading microbes that enter via adjacent infection-prone areas. This review updates recent human studies in light of the current literature and adds information about chemokine gene expression.Materials and Methods: We analyzed surgically obtained human tissue using immunohistochemistry, confocal microscopy, and multichannel super-resolution structured illumination microscopy. The samples were considered representative of steady-state conditions. Antibodies against the ionized calcium-binding adaptor molecule 1 were used to identify the macrophages. CD68 and CD11b, and the major histocompatibility complex type II (MHCII) and CD4 and CD8 were analyzed. The RNAscope technique was used for fractalkine gene localization.Results: Many macrophages were found around blood vessels in the stria vascularis but not CD4 and CD8 lymphocytes. Amoeboid macrophages were identified in the spiral ganglion with surveilling “antennae” projecting against targeted cells. Synapse-like contacts were seen on spiral ganglion cell bodies richly expressing single CXC3CL gene transcripts. Branching neurite-like processes extended along central and peripheral axons. Active macrophages were occasionally found near degenerating hair cells. Some macrophage-interacting T lymphocytes were observed between the scala tympani wall and Rosenthal's canal. CD4 and CD8 cells were not found in the organ of Corti.Conclusions: The results indicate that the human cochlea is equipped with macrophages and potentially lymphocytes, suggesting both an innate and adaptive immune capacity. A rich expression of fractalkine gene transcripts in spiral ganglion neurons suggest an essential role for auditory nerve protection, as has been demonstrated experimentally. The findings provide further information on the important role of the immune machinery present in the human inner ear and its potential to carry adverse immune reactions, including cytotoxic and foreign body responses. The results can be used to form a rationale for therapies aiming to modulate these immune activities.

Endomicroscopy of the human cochlea using a micro-optical coherence tomography catheter

Sensorineural hearing loss (SNHL) is one of the most profound public health concerns of the modern era, affecting 466 million people today, and projected to affect 900 million by the year 2050. Advances in both diagnostics and therapeutics for SNHL have been impeded by the human cochlea’s inaccessibility for in vivo imaging, resulting from its extremely small size, convoluted coiled configuration, fragility, and deep encasement in dense bone. Here, we develop and demonstrate the ability of a sub-millimeter-diameter, flexible endoscopic probe interfaced with a micro-optical coherence tomography (μOCT) imaging system to enable micron-scale imaging of the inner ear’s sensory epithelium in cadaveric human inner ears.

Two Photon Fluorescence Microscopy of the Unstained Human Cochlea Reveals Organ of Corti Cytoarchitecture

Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, and it typically originates from the cochlea. Methods to visualize intracochlear cells in living people are currently lacking, limiting not only diagnostics but also therapies for SNHL. Two-photon fluorescence microscopy (TPFM) is a high-resolution optical imaging technique. Here we demonstrate that TPFM enables visualization of sensory cells and auditory nerve fibers in an unstained, non-decalcified adult human cochlea.

Variations in Microanatomy of the Human Modiolus: Implications for Cochlear Implants

Human cochlear anatomy is highly variable. The phenomenon has been first described qualitatively, followed by a quantitative variability assessment with detailed anatomical models of the human cochlea. However, all previous work focused on lateral cochlear wall. Few information is available on the variability of the modiolar wall. Modiolar variability, likely determined by variability in the spiral ganglion, provides key information on when during ontogenesis the individual cochlear morphology is established: before and/or after neuronal structures are formed. In the present study we analyzed 108 corrosion casts, 95 clinical cone beam computer tomographies and 15 µCTs of human cochleae and observed modiolar variability of similar and larger extent than the lateral wall variability. Lateral wall measures correlated with modiolar wall measures significantly. ~49% of the variability has a common cause, very likely established already during the time when the spiral ganglion is formed. Proximity of other neuronal and vascular structures, defining the remaining variability in scalar spaces, are determined later in ontogenesis, when the scalae are formed. The present data further allows implications for perimodiolar cochlear implants and their tip fold-overs. In particular, the data demonstrate that tip fold-overs of preformed implants likely result from the morphology of the modiolus (with radius changing from base to apex), and that optimal cochlear implantation of perimodiolar arrays cannot be guaranteed without an individualized surgical technique.

Insights into the Pathobiology of TMPRSS3-Related Hearing Loss and Implications for Cochlear Implant Patients with TMPRSS3 Mutations.

OBJECTIVES To review the audiological outcomes after cochlear implantation (CI) for TMPRSS3-associated autosomal recessive non-syndromic hearing loss (ARNSHL) and evaluate the spatial expression pattern of TMPRSS3 within the human cochlea. METHODS Review all published cases of CI in patients with TMPRSS3-associated ARNSHL to compare postoperative consonant-nucleus-consonant (CNC) word performance to published adult CI cohorts. Protein structural modeling of TMPRSS3 variants associated with post-lingual hearing loss. Determine TMPRSS3 expression pattern in human inner ear organoids and human cochlea. RESULTS Nine articles detailed 27 patients (30 total CI ears) with TMPRSS3-associated hearing loss treated with CI. Of these, 6 cases reported prelingual onset (< 2yo) and 24 cases reported post-lingual onset (≥2yo) of hearing loss. Subjectively, 85% of cases had a favorable outcome. Objectively, the postoperative mean (SD) post-operative CNC word score was not significantly different than other adults [66.2% (25.8%) correct vs. 50.1% (12.5%); F(1,6) = 1.97, P = 0.21]. In the TMPRSS3 cohort, poor performers (CNC < 30% correct) were significantly older than good performers [49 (± 13.3) years vs. 17.4 (± 18.4) years; P < 0.01] and all harbored the A138E variant. TMPRSS3 immunostaining is restricted to the otic epithelial cells and is not expressed within auditory neurons of human cochlea and human inner ear organoids. CONCLUSIONS Patients with TMPRSS3-related hearing loss exhibit similar postoperative performance to other adult CI patients. TMPRSS3 is not expressed in human auditory neurons and the duration of hearing loss prior to CI likely contributes to poor performance.

Image Processing of Conventional Computer Tomography Images for Segmentation of the Human Cochlea

Against the background of increasing numbers of indications for Cochlea implants (CIs), there is an increasing need for a CI outcome prediction tool to assist the process of deciding on the best possible treatment solution for each individual patient prior to intervention. The hearing outcome depends on several features in cochlear structure, the influence of which is not entirely known as yet. In preparation for surgical planning a preoperative CT scan is recorded. The overall goal is the feature extraction and prediction of the hearing outcome only based on this conventional CT data. Therefore, the aim of our research work for this paper is the preprocessing of the conventional CT data and a following segmentation of the human cochlea. The great challenge is the very small size of the cochlea in combination with a fairly bad resolution. For a better distinction between cochlea and surrounding tissue, the data has to be rotated in a way the typical cochlea shape is observable. Afterwards, a segmentation can be performed which enables a feature detection. We can show the effectiveness of our method compared to results in literature which were based on CT data with a much higher resolution. A further study with a much larger amount of data is planned.