Gentamicin is Primarily Localized in Vestibular Type I Hair Cells after Intratympanic Administration

Abstract

Intratympanic (IT) gentamicin injections are effective in the control of episodic vertigo due to Ménière's disease. Histological studies in animals have found that the loss of type I vestibular hair cells far exceeds that of type II cells after IT gentamicin treatment. The objective of this study was to determine whether this selective toxicity for type I hair cells might be due to selective concentration of the drug by these cells. Gentamicin was localized within the vestibular epithelium by both direct and indirect methods. Gentamicin conjugated to Texas Red(R) was used as a direct tracer, and anti-gentamicin antibody provided an indirect means of localization. Conjugated or unconjugated gentamicin was injected into the left tympanic space of chinchillas. The animals were killed and fixed 1 or 3 weeks post-treatment. Confocal fluorescence microscopy was used to determine the localization of gentamicin in semicircular canal cristae. Results from the animals killed within 1 week of administration showed that numerous type I hair cells still remained throughout the epithelium. The mean intensity in grayscale units (0-255) of anti-gentamicin labeling for type I hair cells was 28.14 (95% CI 24.60-31.69), for type II hair cells was 17.09 (14.99-19.20), and for support cells was 5.35 (5.34-5.46; p < 0.001, ANOVA). Anti-gentamicin antibody labeling appeared in the majority of type I hair cells throughout their cytoplasm, but with greater intensity at the apex (p < 0.001). Intensity of fluorescence with Texas-Red conjugated gentamicin was 25.38 (22.83-27.94) in type I hair cells, 15.60 (14.73-16.48) in type II cells, and 12.62 (12.06-13.17) in support cells (p < 0.001, ANOVA). These results suggest that type I hair cells are more susceptible to gentamicin because they more avidly take up or retain the drug in the early period after administration.