Characterization of ototoxic-induced prestin burst in the blood and implications for developing prestin as an ototoxicity biomarker

Abstract

In the clinical realm, we primarily rely on audiological measures for diagnosis and surveillance of sensorineural hearing loss (SNHL) and have limited therapeutic options. We have proposed a blood-based biomarker approach to overcome this challenge by measuring the outer hair cell’s (OHC) electromotile protein, prestin, in the blood. In a guinea pig model of cyclodextran (CDX) ototoxicity, using western blots, we show that prestin in the blood may have several different forms and specifically the ~ 134 kDa form spikes after ototoxin ablation of OHCs. This form appears to be a glycosylated dimer likely secreted by the inner ear as exosomes reflecting increased expression after ototoxin exposure. These results suggest that the ~ 134 kDa dimer may serve as a biomarker for early detection of ototoxicity in the clinical setting. However, because prestin can still be measured in the blood after total ablation of OHCs, its ability to inform on OHC health is restricted to a narrow window after ototoxin-induced injury. Monitoring prestin, when using therapeutics with ototoxic properties, could guide dosage and administration schedule to minimize damage.