An In Vivo Model As An Approach To Deliver Potential Therapies For Noise-Induced Hair Cell Loss

Hypothesis Our aim was to develop a minimally invasive approach for continuous delivery of therapeutics to the mouse cochlea.

Background: Techniques for cochlear drug delivery include systemic injection, trans-tympanic injection, endolymphatic sac injection, cochleostomy with perilymphatic perfusion and most recently round-window application.

Methods Using a retrosigmoid approach, a hole was drilled into the posterior semi-circular canal of FVB mice (n = 36 mice) and a catheter attached to a micro-osmotic pump (1 ul/ hour, 3 days), was inserted. Fibrant sealant and fascia closed the opening. The pump, containing either an antioxidant plus DMSO or DMSO alone, was placed subcutaneously on the back. 100 dB SPL noise was presented for 30 minutes. Preoperative, post-noise and 14 days postoperative ABR testing at 8, 12, 16 and 24 kHz was performed for both ears.

Results ABR thresholds pre- and post-noise exposure were compared between mice which were treated with one of six antioxidants plus DMSO, versus mice treated with DMSO alone. Pump insertion did not affect thresholds.

Significantly threshold recovery was observed post-noise for mice treated with one of the antioxidants.

Conclusions The semi-circular canal delivery model, used previously for acute, one-time delivery, presents a reliable approach for continuous drug delivery to the cochlea.

Poster-PDF A-1082.PDF

Publikationsverlauf

Artikel online veröffentlicht:
10. Juni 2020