Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice.
10.13201/j.issn.2096-7993.2024.01.008
- Author:
Zijing WANG
1
;
Qi CAO
1
;
Shaowei HU
2
;
Xintai FAN
2
;
Jun LV
2
;
Hui WANG
2
;
Wuqing WANG
2
;
Huawei LI
2
;
Yilai SHU
1
Author Information
1. Department of Otolaryngology，Second Affiliated Hospital of South China University Hengyang，421001，China.
2. Otolaryngology Department of Fudan University Affiliated Eye，Ear，Nose and Throat Hospital.
- Publication Type:Journal Article
- Keywords:
OTOF;
auditory brainstem response;
distortion product otoacoustic emissions;
gene therapy
- MeSH:
Mice;
Animals;
Otoacoustic Emissions, Spontaneous/physiology*;
Hearing/physiology*;
Ear, Inner;
Hearing Loss/therapy*;
Genetic Therapy;
Auditory Threshold/physiology*;
Evoked Potentials, Auditory, Brain Stem/physiology*;
Membrane Proteins
- From:
Journal of Clinical Otorhinolaryngology Head and Neck Surgery
2024;38(1):49-56
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating 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-mediated 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 expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds 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 function 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 surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
