Nox3, a multi-subunit NADPH oxidase, is functionally and structurally related to Nox1 and Nox2. It belongs to the NOX family of NADPH oxidases, which are responsible for transporting electrons across the plasma membrane to generate superoxide and other reactive oxygen species (ROS) [3,4,6]. Nox3 is essential for otoconia biosynthesis in rodents, and its expression is associated with the development of different types of sensorineural hearing loss (SNHL) [1,2].

Using Nox3-Cre knock-in mice, researchers found that Nox3-expressing cells in the cochlea include various supporting cells, outer and inner hair cells, and spiral ganglion neurons. Nox3 expression increased with cisplatin, age, and noise insults, and its inhibition in the cochlea could be a promising strategy for ROS-related SNHL. For example, knockdown of Nox3 by siRNA pretreatment prevented cisplatin ototoxicity, preserving hearing thresholds and inner ear sensory cells [1,5]. Intracochlear delivery of Nox3-siRNAs also induced significant Nox3 downregulation, which may prevent acute insults like cisplatin-mediated ototoxicity and other forms of acquired hearing loss [7].

In conclusion, Nox3 plays a crucial role in otoconia formation and is strongly associated with sensorineural hearing loss. Studies using Nox3-KO/CKO mouse models and siRNA-mediated knockdown have provided valuable insights into its function, highlighting its potential as a therapeutic target for preventing or treating hearing loss related to cisplatin, aging, and noise exposure.