Journal
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
Volume 8, Issue 4, Pages 497-508Publisher
SPRINGER
DOI: 10.1007/s10162-007-0093-8
Keywords
aminoglycoside; ototoxicity; Meniere disease; endolymphatic hydrops
Categories
Funding
- NEI NIH HHS [P30 EY001765] Funding Source: Medline
- NIDCD NIH HHS [R03 DC05700, K08 DC0062160, R03 DC005700, K23 DC00196, T32 DC00027, P30 DC005211, T32 DC000027, K23 DC000196] Funding Source: Medline
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Intratympanic (IT) gentamicin injections are effective in the control of episodic vertigo due to Menier's disease. Histological studies in animals have found that the loss of type I vestibular hair cells far exceeds that of type 11 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 Redo 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 I 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 I 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% Cl 24.60-31.69), for type 11 hair cells was 17.09 (14.99-19.20), and for support cells was 5.35 (5.345.46; 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 11 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.
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