TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation

Abstract

BackgroundIt is well established that biallelic mutations in transmembrane protease, serine 3 (TMPRSS3) cause hearing loss. Currently, there is controversy regarding the audiological outcomes after cochlear implantation (CI) forTMPRSS3-associated hearing loss. This controversy creates confusion among healthcare providers regarding the best treatment options for individuals withTMPRSS3-related hearing loss.MethodsA literature review was performed to identify all published cases of patients withTMPRSS3-associated hearing loss who received a CI. CI outcomes of this cohort were compared with published adult CI cohorts using postoperative consonant-nucleus-consonant (CNC) word performance.TMPRSS3expression in mouse cochlea and human auditory nerves (HAN) was determined by using hybridisation chain reaction and single-cell RNA-sequencing analysis.ResultsIn aggregate, 27 patients (30 total CI ears) withTMPRSS3-associated hearing loss treated with CI, and 85% of patients reported favourable outcomes. Postoperative CNC word scores in patients withTMPRSS3-associated hearing loss were not significantly different than those seen in adult CI cohorts (8 studies). RobustTmprss3expression occurs throughout the mouse organ of Corti, the spindle and root cells of the lateral wall and faint staining within <5% of the HAN, representing type II spiral ganglion neurons. Adult HAN express negligible levels ofTMPRSS3.ConclusionThe clinical features after CI and physiological expression ofTMPRSS3suggest against a major role of TMPRSS3 in auditory neurons.