Distribution of macrophages in the cochlea following radiation-induced sensorineural hearing loss

Radiation-induced sensorineural hearing loss (RISNHL) is a common and irreversible complication of radiotherapy for head and neck tumors, with currently no effective treatment. While traditional research has primarily focused on the direct effects of radiation on cochlear hair cells (HCs), this alone does not explain the early onset of hearing loss observed before HC degeneration. Emerging evidence from our preliminary study suggests that the pathogenesis of RISNHL may be driven by significant microenvironmental alterations within the cochlea, particularly involving dysfunction of the stria vascularis (SV) and changes in macrophage activity. However, the precise mechanisms underlying radiation-induced cochlear damage remain unclear. In this study, we investigated the dynamic changes in cochlear macrophages from 2 to 20 weeks (w) following ionizing radiation (IR). Our results revealed a time-dependent increase in IBA1-positive macrophages in both the cochlear lateral wall and spiral ganglion, peaking between 12 and 20 w. Further analysis showed significant macrophage accumulation and activation in the SV region following localized irradiation. Proteomic profiling identified upregulated expression of ADAM17 in the SV at both 1 and 8 w post-IR, indicating a potential role for immune processes in radiation-induced cochlear injury. These findings highlight the critical role of macrophages in post-radiation cochlear damage. Our study systematically characterizes the spatiotemporal progression of radiation-induced cochlear damage and offers insights into novel intervention strategies that could be applied before irreversible HC loss occurs.