(0926) Elucidating the Role of TGF-β Signaling in Kanamycin-Induced Inner Ear Damage

Introduction: Transforming growth factor-β (TGF-β) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact in the cochlea remains unclear. We aimed to investigate the effects of TGF-β signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity.

Methods: Kanamycin (200 mg/kg) and furosemide (400 mg/Kg) (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-β receptor inhibitor (TGF-βRI) on the round window membrane. ABR was performed to measure the hearing thresholds of mice before, 14 days after, and 28 days after KM-FS administration. TGF-β expression was evaluated using the Mouse TGF-β ELISA kit at 3, 7, and 14 days after KM-FS administration. The cochleae were dissected 7, 14, and 28 days after KM-FS administration and evaluated immunohistochemically for TGF-β receptor expressions, hair cell survival, spiral ganglion neurons (SGNs) survival, and macrophage infiltration in the SGNs.

Results: Significant TGF-β receptor upregulation in SGNs after KM-FS ototoxicity, whereas significant downregulation was observed following TGF-βRI treatment (p < 0.05). Despite no significant change in cochlear TGF-β expression after KM-FS ototoxicity (p > 0.05), TGF-βRI treatment resulted in a significant decrease in signaling (p < 0.05). Regarding auditory function, TGF-βRI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-βRI treatment (p < 0.05).

Conclusions: TGF-β signaling inhibition after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.