Establishment of a model of cochlear lesions in rats to study potential gene therapy for sensorineural hearing loss

Abstract

IntroductionSensorineural hearing loss seriously influences a patient's daily life, and no effective treatments exist to date. Gene therapy is a potential treatment for regenerating hair cells to restore hearing. MethodsIn this study, we established a cochlear lesions model to study hair cell regeneration by co-administration of kanamycin and furosemide. After the injections, we assessed the survival of outer hair cells (OHC), inner hair cells (IHC), supporting cells (SC), spiral ganglion neurons (SGN) and peripheral axons. Moreover, we used two viral vectors to detect the transgene distribution. ResultsOur results showed at 12h post-treatment, numerous OHC were missing in the basal turn. At 24h post-treatment, all OHCs in basal half of the cochlea were lost, and by 48h, OHC loss had spread to the apical coil. Four days after the injections, all OHCs were absent. At 1mo post-treatment, the organ of Corti had collapsed. In contrast, most of the SC remained 4d after the injections. The loss of SGN and peripheral axons was consistent with this time course post-treatment. The results of transgene distribution suggested the correlative gene can be transferred into the organ of Corti using adenoviruses (AdV) vectors and lentiviruses (LV) vectors in our cochlear lesion model.Comparison with Existing Method(s): We assessed the details of HC death at more time point and chosen the time point for gene transfer in this model. ConclusionsWe conclude that this cochlear lesion model would be suitable for the study of hair cell regeneration.