Intra-tympanic delivery of short interfering RNA into the adult mouse cochlea

Oishi, Naoki; Chen, Fu Quan; Zheng, Hong; Sha, Su Hua

doi:10.1016/j.heares.2012.10.011

Cited by 35 publications

(28 citation statements)

References 21 publications

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“…Finally, we assessed the ability of LC3B siRNA (siLC3B) to decrease autophagosome formation under TTS-noise conditions. siLC3B was delivered locally to the round window (7,37). Two concentrations of siLC3B, 0.3 and 0.6 lg, were tested.…”

Section: Fig 2 Noise Exposure Alters the Expression Of 3-nt And 4-nmentioning

confidence: 99%

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Autophagy Attenuates Noise-Induced Hearing Loss by Reducing Oxidative Stress

Wang

Hill

et al. 2015

Antioxidants & Redox Signaling

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Section: Fig 2 Noise Exposure Alters the Expression Of 3-nt And 4-nmentioning

confidence: 99%

“…Intratympanic delivery of siRNA siLC3B (Invitrogen, Carlsbad, CA) or siControl (Invitrogen) was locally delivered via intra-tympanic application. We followed the procedures as previously described (7,37).…”

Section: Drug Administration Via Intra-peritoneal Routementioning

confidence: 99%

Autophagy Attenuates Noise-Induced Hearing Loss by Reducing Oxidative Stress

Wang

Hill

et al. 2015

Antioxidants & Redox Signaling

Self Cite

134

145

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“…The methods for small-interfering RNA (siRNA) delivery into the adult mouse inner ear in vivo were modified from a recent study (Oishi et al 2013). Briefly, after anesthesia, a retroauricular incision was made to approach the temporal bone.…”

Section: Intra-tympanic Delivery Of Sirnamentioning

confidence: 99%

Inhibitors of Histone Deacetylases Attenuate Noise-Induced Hearing Loss

Chen

Hill

Sha

2016

JARO

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Loss of auditory sensory hair cells is the major pathological feature of noise-induced hearing loss (NIHL). Currently, no established clinical therapies for prevention or amelioration of NIHL are available. The absence of treatments is due to our lack of a comprehensive understanding of the molecular mechanisms underlying noise-induced damage. Our previous study indicates that epigenetic modification of histones alters hair cell survival. In this study, we investigated the effect of noise exposure on histone H3 lysine 9 acetylation (H3K9ac) in the inner ear of adult CBA/J mice and determined if inhibition of histone deacetylases by systemic administration of suberoylanilide hydroxamic acid (SAHA) could attenuate NIHL. Our results showed that H3K9ac was decreased in the nuclei of outer hair cells (OHCs) and marginal cells of the stria vascularis in the basal region after exposure to a traumatic noise paradigm known to induce permanent threshold shifts (PTS). Consistent with these results, levels of histone deacetylases 1, 2, and 3 (HDAC1, HDAC2 and HDAC3) were increased predominately in the nuclei of cochlear cells. Silencing of HDAC1, HDAC2, or HDAC3 with siRNA reduced the expression of the target HDAC in OHCs, but did not attenuate noise-induced PTS, whereas treatment with the pan-HDAC inhibitor SAHA, also named vorinostat, reduced OHC loss, and attenuated PTS. These findings suggest that histone acetylation is involved in the pathogenesis of noise-induced OHC death and hearing loss. Pharmacological targeting of histone deacetylases may afford a strategy for protection against NIHL.

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“…The methods for siRNA delivery into the adult mouse inner ear in vivo were modified from a recent study (Oishi et al 2013). Briefly, after anesthesia, a retroauricular incision was made to approach the temporal bone.…”

Section: Intra-tympanic Delivery Of Sirnamentioning

confidence: 99%

Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling

Chen

Talaska

et al. 2015

JARO

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The PI3K/Akt signaling pathway is involved in mediating survival of sensory hair cells. Here, we investigated the involvement of PI3K/Akt in noise-induced hearing loss in both temporary and permanent threshold shift noise models. The PI3K regulatory subunit p85α and phosphorylation of Akt on serine 473 (p-Akt S473) are downregulated in sensory hair cells, including both outer and inner hair cells, and supporting cells of the mouse organ of Corti 1 h after exposure to permanent-threshold-shift-inducing noise (PTS noise), but not with temporary-threshold-shiftinducing noise (TTS noise). In contrast, the PI3K catalytic subunit p110α and phosphorylation of Akt on threonine 308 (p-Akt T308) do not change with PTS or TTS noise. Additionally, mice pretreated with p85α small interfering RNA (siRNA) have decreased expression of p-Akt1 (S473) in their sensory hair cells and increased sensitivity to TTS noise-induced hearing loss. Finally, Akt1-knockout mice also have enhanced sensitivity to TTS noise-induced hearing loss. In conclusion, this study suggests that endogenous PI3K/Akt signaling is an intrinsic protective mechanism of the inner ear. Blockade of PI3K/Akt signaling pathways increases sensitivity to TTS noise-induced hearing loss.

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Intra-tympanic delivery of short interfering RNA into the adult mouse cochlea

Cited by 35 publications

References 21 publications

Autophagy Attenuates Noise-Induced Hearing Loss by Reducing Oxidative Stress

Autophagy Attenuates Noise-Induced Hearing Loss by Reducing Oxidative Stress

Inhibitors of Histone Deacetylases Attenuate Noise-Induced Hearing Loss

Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling

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