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Dose-related vestibular and cochlear effects of transtympanic gentamicin
H H Wanamaker1, L Gruenwald, K J Damm
1Department of Bioengineering and Neuroscience, Institute for Sensory Research, Syracuse University, New York, USA.
Hypothesis:
To test the relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected gentamicin in the Mongolian gerbil.
Background:
Transtympanic gentamicin is gaining favor as a relatively noninvasive treatment for Meniere's disease (MD). Few basic science studies exist regarding the vestibular and cochlear toxicities and dosage and administration schedules, however. The absence of standardized procedures and use of different species as animal models may account for the variable outcomes and lack of agreement found in the literature.
Methods:
Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1x) and five (5x) daily injections of gentamicin/gelfoam slurry and similarly injected (saline/gelfoam) and noninjected controls.
Results:
Two weeks after injection, qualitative and quantitative changes were seen in posterior cristae hair cells in the 1x and 5x gentamicin injected groups. Statistically significant decreases in hair cells were seen when 5x injected ears were compared with 1x injected ears and when 1x injected ears were compared with control ears. When damage was observed in the posterior crista sensory cells, damage was also seen in cochlear hair cells.
Conclusions:
Our results suggest that in the gerbil, gentamicin is ototoxic but not selectively vestibulotoxic. In general, increasing the number of transtympanic injections increases the damage to sensory hair cells in both the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in both cochlear and vestibular hair cells from the same animal.
Insights
Gentamicin injections for Meniere
Area of Science:
- Ototoxicity research
- Inner ear physiology
- Pharmacology
Background:
- Transtympanic gentamicin is an emerging treatment for Meniere's disease (MD).
- Limited basic science data exists on gentamicin's cochlear and vestibular toxicities.
- Variability in study outcomes may stem from non-standardized methods and animal models.
Purpose of the Study:
- To evaluate the dose-dependent cochlear and vestibular ototoxicity of transtympanic gentamicin.
- To compare ototoxicity from single (1x) versus multiple (5x) daily injections in gerbils.
Main Methods:
- Histological examination of inner ear tissues from Mongolian gerbils.
- Comparison of gentamicin-injected groups (1x and 5x) with saline-injected and non-injected controls.
- Assessment of hair cell damage in the posterior crista and cochlea.
Main Results:
- Both 1x and 5x gentamicin injections caused hair cell damage in the posterior crista.
- Significant hair cell loss was observed with increasing injection frequency (5x > 1x > control).
- Cochlear hair cell damage correlated with vestibular damage in the same animal.
Conclusions:
- Gentamicin is ototoxic in gerbils, affecting both vestibular and cochlear systems.
- Increased injection frequency exacerbates sensory hair cell damage.
- Individual susceptibility varies, but cochlear and vestibular damage are consistent within an animal.
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