Hough, Kate, Nichani, Jaya, Findlay, Callum Andrew, Bruce, Iain A. and Newman, Tracey (2025) Understanding the role of middle ear macrophages in profoundly deaf children; the potential to improve hearing with cochlear implants. GLIA, 73 (S1), E233-E1364. (doi:10.1002/glia.70038).
Abstract
Background: middle ear infection and inflammation (otitis media) is the leading cause of hearing loss worldwide. A history of childhood otitis media increases the risk of hearing loss in adulthood [1] and can affect outcomes following cochlear implantation [2]. Cochlear implants are a life changing intervention for profoundly deaf children. Unfortunately, many children don’t achieve the expected benefits of their implant [3]. A variable tissue, or fibrotic, response to implantation may be factor [4] however this is not well understood. Pre-clinical and temporal bone [5] studies have shown that middle ear infection causes inflammation and damage within the cochlea associated with changes in macrophages [6]. However, there is little understanding of the role of macrophages in how well children hear with a cochlear implant.
We hypothesise that the activation state of middle ear macrophages differs between children undergoing cochlear implantation due to their varying immune history [7,8].
This study aims to determine whether immune biology of the middle ear is a biological factor contributing to underperformance in children with cochlear implants.
Methods: CHIEF (cochlear implants and inner ear inflammation)[9] is a cross-sectional study of children and young people undergoing cochlear implantation. Samples of the middle ear mucosa and cochlear fluid will be collected during surgery. Following implantation, routine clinical outcome measures and health data will be collected for up to five years.
We will use CosMx [10], a spatial transcriptomics platform, to characterise the spatial gene expression of the macrophages in the middle ear of children undergoing cochlear implantation, for the first time. We will use bioinformatic analysis to determine if there are differences in gene expression of the macrophages within and between samples and determine what cells the macrophages are communicating with.
Conclusion: this work will provide new knowledge of the immune biology of the ear in children undergoing implantation and inform our understanding of biological factors that can influence hearing outcomes with an implant. Through CHIEF, we will generate a database containing clinical and medical history of children undergoing cochlear implantation and a tissue bank. We will analyse the relationship between the biological and clinical data (collected over five years) to interrogate how the immune state of the ear is associated with long-term hearing outcomes. If a predictable relationship is determined, there is potential to improve long-term hearing outcomes in children following implantation by modulating inflammation, using anti-inflammatory therapies.
References
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3 Cupples L, Ching TYC, Button L, et al. Language and speech outcomes of children with hearing loss and additional disabilities: identifying the variables that influence performance at five years of age. Int J Audiol. 2018;57:S93–104. doi: 10.1080/14992027.2016.1228127
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7 Hough K, Verschuur CA, Cunningham C, et al. Macrophages in the cochlea; an immunological link between risk factors and progressive hearing loss. Glia. 2021;1–20. doi: 10.1002/glia.24095
8 Cunningham C, Wilcockson DC, Campion S, et al. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. Journal of Neuroscience. 2005;25:9275–84. doi: 10.1523/JNEUROSCI.2614-05.2005
9 Hough K, Nichani J, Findlay C, et al. Protocol for CHIEF (cochlear implants and inner ear inflammation) study; an observational, cross-sectional, study of children and young people undergoing cochlear implantation [Preprint]. MedXRiv. Published Online First: 26 November 2024. doi: 10.1101/2024.11.25.24317767
10 He S, Bhatt R, Brown C, et al. High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging. Nat Biotechnol. 2022;40:1794–806. doi: 10.1038/s41587-022-01483-z
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