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Updated: Aug 18, 2026
The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
Cochlear hair cell loss in single-dose versus continuous round window administration of gentamicin
Niels Wagner1, Per Cayé-Thomasen, Göran Laurell
1Department of Otorhinolaryngology, Gentofte University Hospital of Copenhagen, Hellerup, Denmark.
Conclusions:
Gentamicin-induced cochlear hair cell loss depends on local middle ear administration kinetics and the total drug dose. Single-dose gentamicin instillation in the middle ear is associated with a high variation in hair cell loss.
Objective:
To compare the effects of single-dose and continuous round window administration of gentamicin on cochlear hair cell loss in a guinea pig model.
Material And Methods:
Two methods for drug administration to the inner ear were used. In groups of five animals, a total dose of 0.8 or 3.2 mg of gentamicin was either instilled as a single dose directly into the round window niche or administered continuously over a 1-week period using a pump-catheter system. Continuous administration was achieved by means of a posterior tympanotomy and subcutaneous placement of an osmotic pump fitted with a catheter. The tip of the catheter was fixed in the round window niche. One group of five animals served as controls and received a saline infusion. The animals were sacrificed after 1 week and hair cell loss was determined microscopically after dissection and phalloidin labelling of the basilar membrane and organ of Corti.
Results:
Quantitation of cochlear hair cell loss revealed a dose-dependent effect of gentamicin. With both treatment modalities the higher dose induced a higher percentage of hair cell loss. There was inner and outer hair cell loss in all four groups that received gentamicin. With the single-dose instillation, hair cell loss was distributed irregularly from the round window membrane towards the cochlear apex, whereas continuous administration induced hair cell loss close to the round window membrane. Single-dose instillation induced greater hair cell loss than continuous administration at the same dose. The inter-individual variation in hair cell loss was highest following single-dose instillation.
Insights
Single-dose gentamicin instillation causes variable cochlear hair cell loss. Continuous administration over one week results in less damage and more predictable outcomes for inner ear treatments.
Area of Science:
- Ototoxicity research
- Inner ear drug delivery
- Auditory system science
Background:
- Gentamicin is an ototopical antibiotic used to treat inner ear diseases.
- Understanding gentamicin's effects on cochlear hair cells is crucial for optimizing treatment strategies.
- Variability in drug administration can significantly impact ototoxicity.
Purpose of the Study:
- To compare the ototoxic effects of single-dose versus continuous round window administration of gentamicin.
- To evaluate cochlear hair cell loss in a guinea pig model under different gentamicin delivery conditions.
- To assess the influence of administration kinetics on gentamicin-induced ototoxicity.
Main Methods:
- Gentamicin was administered to guinea pigs either as a single dose or continuously over one week via a pump-catheter system targeting the round window niche.
- Two total doses (0.8 mg and 3.2 mg) were tested for both administration methods.
- Cochlear hair cell loss was quantified microscopically after phalloidin labeling of the basilar membrane and organ of Corti.
Main Results:
- Gentamicin-induced hair cell loss was dose-dependent, with higher doses causing greater loss.
- Single-dose instillation resulted in more significant and irregularly distributed hair cell loss compared to continuous administration.
- Continuous administration led to localized hair cell loss near the round window and exhibited lower inter-individual variation.
Conclusions:
- Cochlear hair cell loss from gentamicin is influenced by both the total dose and the method of middle ear administration.
- Single-dose gentamicin instillation into the middle ear leads to unpredictable and often severe hair cell loss.
- Continuous round window administration offers a more controlled approach to gentamicin delivery, potentially minimizing ototoxicity.
