Sensory Hair Cells of the Inner Ear Can Repair Themselves to Some Degree

Hearing loss involves either damage or loss of sensory hair cells in the inner ear, or loss of their connections to the brain. It remains somewhat unclear as to whether cell damage, cell death, or connection loss is the primary mechanism of interest in mammals. Researchers here investigate the way in which hair cells repair themselves. Where a mechanism like this exists and is understood, there is the potential to increase its efficiency as a basis for therapy. This may prove to be a useful treatment for some forms of deafness, but only those in which the cells and their connections remain, where hearing loss results from unrepaired structural damage to the hair cells.

The long-term maintenance of sensory hair cells faces a fundamental challenge: to maximize sensitivity, hair cells are built to be delicate and fragile, yet they have to withstand continuous mechanical stress. A potent capacity for repair must therefore be considered indispensable, especially for mammalian auditory hair cells that are not regenerated. In our study, we provide evidence for a novel process that repairs lesions in the stereocilia F-actin core. The damaged sites can be visualized as 'gaps' in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments.

Herein, we show that gaps in mouse auditory hair cells are largely repaired within 1 week of traumatic noise exposure through the incorporation of newly synthesized actin. We provide evidence that Xin actin binding repeat containing 2 (XIRP2) is required for the repair process and facilitates the enrichment of monomeric γ-actin at gaps. Recruitment of XIRP2 to stereocilia gaps and stress fiber strain sites in fibroblasts is force-dependent, mediated by a novel mechanosensor domain located in the C-terminus of XIRP2. Our study describes a novel process by which hair cells can recover from sublethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss.

Link: https://doi.org/10.7554/eLife.72681