Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/-mice
Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emis-sions(DPOAE)and auditory brainstem response(ABR)in adult Otof-/-mice before and after gene therapy,e-valuating its effectiveness and exploring methods for assessing hearing recovery post-treatment.Methods:At the age of 4 weeks,adult Otof-/-mice received an inner ear injection of a therapeutic agent containing intein-media-ted recombination of the OTOF gene,delivered via dual AAV vectors through the round window membrane(RWM).Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin ex-pression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresh-olds before and after the treatment.Results:AAV-PHP.eB demonstrates high transduction efficiency in inner ear hair cells.The therapeutic regimen corrected hearing loss in adult Otof-/-mice without impacting auditory func-tion in wild-type mice.The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz.Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment.Conclusion:Gene therapy significantly restored hearing in adult Otof-/-mice,though the surgi-cal delivery may cause transient hearing damage.Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
NETL
NSTL
万方数据
