Hearing loss (HL) is one of the most common sensory impairments. Acquired HLs, such as age-related (ARHL), noise-induced, and drug-induced HL, are classified based on the underlying mechanism. The most common form of sensorineural HL (SNHL) is ARHL, affecting 25~40% of individuals over 65 years of age. Noise is one of the most common occupational hazards. In 2019, WHO warned that half of young people risk damaging their hearing through excessive use of audio devices. However, treatment options for SNHL rely on medical instruments, with no reliable pharmacological interventions.
Nox family is one of the main sources of reactive oxygen species (ROS). Recently, we have reported transgenic mice expressing NOX4 exhibit hearing vulnerability after noise exposure, demonstrating ROS contribute to SNHL. Nox3, activated by a Rho-family GTPase Rac, was discovered as an inner ear specific Nox; however, Nox3-expressing cells were ambiguous. We generated Nox3-Cre;tdTomato mice, in which tdTomato fluorescence is regulated by the Nox3 promoter-driven Cre. Nox3-expressing cells in cochleae included outer hair cells (OHCs) and supporting cells (SCs), and they increased with aging, noise, and cisplatin. Moreover, increased Nox3 expression in OHCs and SCs played essential roles in ROS-related SNHL through OHC apoptosis. Thus, ROS are promising targets for therapeutics development for acquired SNHLs. I will discuss our hearing research focused on ROS and Rho-family GTPases.