Disruption of a Structural Niche for Otoconia Maintenance May Underlie Common Vestibular Disorders
- 1Otopathology Laboratory, Eaton-Peabody Laboratories, Laboratory Mass Eye and Ear - Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School
Abstract
Many falls and balance disorders in older adults originate in the otolith organs, the gravity sensors of the inner ear. These sensors maintain upright posture through otoconia, calcium carbonate crystals that mass-load the sensory maculae. Otoconia dislodgement causes the most common form of vertigo, and their age-related loss reduces gravity sensation and undermines balance. Yet the cellular mechanisms of otoconia formation and maintenance -and how they fail in disease- remain unknown. Using mineral-preserving histology, crystal-sensitive imaging, volume electron microscopy, and immunolabeling in human and animal otolith organs, we found otoconia biogenesis-related proteins and early crystallization at the pole opposing the macula, the roof domain. We discovered filigree extracellular matrix scaffolds bridging roof and macula, loaded with nascent otoconia, suggesting scaffold-guided transport across the organ. Single-cell transcriptomics nominated a specialized roof mesenchyme, signaling to the roof epithelium, as a driver of otoconia and scaffold production. In guinea pigs with endolymphatic hydrops, fluid expansion of the organs ruptured the otoconia-trafficking scaffolds as roof and macula separated, followed by a decline in macular otoconial mass. We propose a new disease model for common vertigo and balance disorders in which disruption of the otoconia-generating and -trafficking epithelial-mesenchymal roof niche leads to displacement and depletion of otoconia.
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BibTeX
@misc{correa2026disruption,
title = {{Disruption of a Structural Niche for Otoconia Maintenance May Underlie Common Vestibular Disorders}},
author = {D. M. Correa and A. P. David and R. Zhou and R. Osgood and A. A. Indzhykulian and S. Kraemer and T. A. Jan and A. H. Eckhard},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.752180},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.752180v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Disruption of a Structural Niche for Otoconia Maintenance May Underlie Common Vestibular Disorders
AU - D. M. Correa
AU - A. P. David
AU - R. Zhou
AU - R. Osgood
AU - A. A. Indzhykulian
AU - S. Kraemer
AU - T. A. Jan
AU - A. H. Eckhard
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.752180
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.752180v1
AB - Many falls and balance disorders in older adults originate in the otolith organs, the gravity sensors of the inner ear. These sensors maintain upright posture through otoconia, calcium carbonate crystals that mass-load the sensory maculae. Otoconia dislodgement causes the most common form of vertigo, and their age-related loss reduces gravity sensation and undermines balance. Yet the cellular mechanisms of otoconia formation and maintenance -and how they fail in disease- remain unknown. Using mineral-preserving histology, crystal-sensitive imaging, volume electron microscopy, and immunolabeling in human and animal otolith organs, we found otoconia biogenesis-related proteins and early crystallization at the pole opposing the macula, the roof domain. We discovered filigree extracellular matrix scaffolds bridging roof and macula, loaded with nascent otoconia, suggesting scaffold-guided transport across the organ. Single-cell transcriptomics nominated a specialized roof mesenchyme, signaling to the roof epithelium, as a driver of otoconia and scaffold production. In guinea pigs with endolymphatic hydrops, fluid expansion of the organs ruptured the otoconia-trafficking scaffolds as roof and macula separated, followed by a decline in macular otoconial mass. We propose a new disease model for common vertigo and balance disorders in which disruption of the otoconia-generating and -trafficking epithelial-mesenchymal roof niche leads to displacement and depletion of otoconia.
ER -