Supporting cell involvement in cochlear damage and repair: Novel insights from a quantitative analysis of cyclodextrin-induced ototoxicity in mice

The cochlea is vulnerable to various pathological conditions, with sensory cells typically being the primary targets of damage. However, supporting cells also experience significant impacts. Despite their critical role in maintaining the structural and functional integrity of the sensory epithelium, the supporting cell involvement in cochlear damage remains poorly understood. This study aimed to elucidate the susceptibility of supporting cells in cochlear damage and their role in structural repair, using a mouse model of ototoxicity induced by cyclodextrin—a cyclic oligomer of glucose that is known to preferentially damage outer hair cells at high doses. A morphological examination of the cochlea showed that cyclodextrin exposure caused significant sensory cell loss, particularly affecting outer hair cells across the cochlear spiral, except at the apex. Despite extensive hair cell damage, most supporting cells in the apical and middle cochlear regions survived. In the basal end, where substantial supporting cell loss occurred, certain Deiters’ cells survived even after losing their phalangeal processes. Additionally, our observations indicate that Hensen's cells contribute to forming an epithelial layer over the basilar membrane when the organ of Corti collapses. Further quantitative analysis revealed location-dependent susceptibility among supporting cell types. Deiters’ cells demonstrated greater resilience than pillar cells. Notably, the three rows of Deiters’ cells displayed differential susceptibility: the third row showed a more significant loss in regions with sporadic Deiters’ cell loss, while the first row exhibited an increased loss in areas adjacent to regions of complete Deiters’ cell depletion. The reduction of Hensen's cells started in the middle section of the cochlea, occurring at a greater level than the reduction observed in Deiters’ and pillar cells. However, in the extreme base, where both pillar and Deiters’ cells were largely or completely absent, some Hensen's cells were still present. Together, these findings provide new insights into the varying vulnerability of supporting cells to cochlear damage and underscore their essential role in structural repair.