TY - JOUR
T1 - Intra-tympanic delivery of short interfering RNA into the adult mouse cochlea
AU - Oishi, Naoki
AU - Chen, Fu Quan
AU - Zheng, Hong Wei
AU - Sha, Su Hua
N1 - Funding Information:
The research project described was supported by grant R01 DC009222 from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health . This work was partially conducted in the Walton Research Building in renovated space supported by grant C06 RR014516. Some animals used in this study were housed in MUSC CRI animal facilities supported by grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources . We thank Dr. Jochen Schacht for his valuable comments on the manuscript.
PY - 2013/2
Y1 - 2013/2
N2 - Trans-tympanic injection into the middle ear has long been the standard for local delivery of compounds in experimental studies. Here we demonstrate the advantages of the novel method of intra-tympanic injection through the otic bone for the delivery of compounds or siRNA into the adult mouse cochlea. First, a fluorescently-conjugated scrambled siRNA probe was applied via intra-tympanic injection into the middle ear cavity and was detected in sensory hair cells and nerve fibers as early as 6 h after the injection. The fluorescent probe was also detected in other cells of the organ of Corti, the lateral wall, and in spiral ganglion cells 48 h after the injection. Furthermore, intra-tympanic delivery of Nox3 siRNA successfully reduced immunofluorescence associated with Nox3 in outer hair cells 72 h after injection by 20%. Drug or siRNA delivery via intra-tympanic injection does not compromise the tympanic membrane or interfere with noise-induced hearing loss, while trans-tympanic injections significantly altered the cochlear response to noise exposure. In summary, intra-tympanic injection through the otic bone into the middle ear cavity provides a promising approach for delivery of compounds or siRNA to cochlear hair cells of adult mice, relevant for the study of mechanisms underlying inner ear insults and, specifically, noise-induced hearing loss.
AB - Trans-tympanic injection into the middle ear has long been the standard for local delivery of compounds in experimental studies. Here we demonstrate the advantages of the novel method of intra-tympanic injection through the otic bone for the delivery of compounds or siRNA into the adult mouse cochlea. First, a fluorescently-conjugated scrambled siRNA probe was applied via intra-tympanic injection into the middle ear cavity and was detected in sensory hair cells and nerve fibers as early as 6 h after the injection. The fluorescent probe was also detected in other cells of the organ of Corti, the lateral wall, and in spiral ganglion cells 48 h after the injection. Furthermore, intra-tympanic delivery of Nox3 siRNA successfully reduced immunofluorescence associated with Nox3 in outer hair cells 72 h after injection by 20%. Drug or siRNA delivery via intra-tympanic injection does not compromise the tympanic membrane or interfere with noise-induced hearing loss, while trans-tympanic injections significantly altered the cochlear response to noise exposure. In summary, intra-tympanic injection through the otic bone into the middle ear cavity provides a promising approach for delivery of compounds or siRNA to cochlear hair cells of adult mice, relevant for the study of mechanisms underlying inner ear insults and, specifically, noise-induced hearing loss.
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U2 - 10.1016/j.heares.2012.10.011
DO - 10.1016/j.heares.2012.10.011
M3 - Article
C2 - 23183031
AN - SCOPUS:84870941644
VL - 296
SP - 36
EP - 41
JO - Hearing Research
JF - Hearing Research
SN - 0378-5955
ER -