Aminoglycosides are toxic to sensory hair cells (HCs). Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. However, the role of autophagy in aminoglycoside-induced HC injury is unknown. Here, we first found that autophagy activity was significantly increased, including enhanced autophagosome-lysosome fusion, in both cochlear HCs and HEI-OC-1 cells after neomycin or gentamicin injury, suggesting that autophagy might be correlated with aminoglycoside-induced cell death. We then used rapamycin, an autophagy activator, to increase the autophagy activity and found that the ROS levels, apoptosis, and cell death were significantly decreased after neomycin or gentamicin injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) or knockdown of autophagy-related (ATG) proteins resulted in reduced autophagy activity and significantly increased ROS levels, apoptosis, and cell death after neomycin or gentamicin injury. Finally, after neomycin injury, the antioxidant N-acetylcysteine could successfully prevent the increased apoptosis and HC loss induced by 3-MA treatment or ATG knockdown, suggesting that autophagy protects against neomycin-induced HC damage by inhibiting oxidative stress. We also found that the dysfunctional mitochondria were not eliminated by selective autophagy (mitophagy) in HEI-OC-1 cells after neomycin treatment, suggesting that autophagy might not directly target the damaged mitochondria for degradation. This study demonstrates that moderate ROS levels can promote autophagy to recycle damaged cellular constituents and maintain cellular homeostasis, while the induction of autophagy can inhibit apoptosis and protect the HCs by suppressing ROS accumulation after aminoglycoside injury.

Tinnitus is believed to result from the maladaptive plasticity of the auditory nervous system; reports regarding its severity and prognosis are conflicting. We evaluated the characteristic and short-term prognosis of tinnitus associated with sudden sensorineural hearing loss (SSNHL). A total of 230 cases were enrolled. The severity and 1-month prognosis of tinnitus (according to the Tinnitus Handicap Inventory (THI)) were assessed in terms of the patients' sex, age, level of hearing loss, type of audiogram results, and so on. According to our statistical analysis, the degree of handicap due to tinnitus was not related to sex, age, or level of hearing loss; the Tinnitus Handicap Inventory indicated that the low-frequency-audiogram group had a low tinnitus handicap (F = 7.516, P = 0.000). Furthermore, we found that the prognosis of tinnitus was not related to the type of audiogram or level of hearing loss. Recovery from a severe level of hearing loss was, however, found to be associated with a poor tinnitus prognosis (F = 5.203, P = 0.006). In summary, our study indicates that the association between tinnitus and SSNHL is extremely high. Tinnitus can be ameliorated by the successful treatment of hearing loss. The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800014797).

The ideal treatment for sensory hearing loss is to regenerate inner ear hair cells (HCs) through stem cell therapy, thereby restoring the function and structure of the cochlea. Previous studies have found that Lgr5+ supporting cells (SCs) in the inner ear can regenerate HCs, thus being considered inner ear progenitor cells. In addition to traditional biochemical factors, physical factors such as electrical conductivity also play a crucial role in the regulation of stem cell proliferation and differentiation. In this study, the graphene substrates were used to culture Lgr5+ progenitor cells and investigated their regulatory effects on cells. It was demonstrated that the graphene substrates displayed great cytocompatibility for Lgr5+ progenitors and promoted their sphere-forming ability. Moreover, more Myosin7a+ cells were found on the graphene substrates compared with tissue culture polystyrene (TCPS). These results suggest that graphene is an efficient interface that can promote the differentiation of Lgr5+ progenitors into HCs, which is great significance for its future application in combination with Lgr5+ cells to regenerate HCs in the inner ear.