title: Temporal and spatial distribution of gentamicin in the peripheral vestibular system after transtympanic administration in guinea pigs.
abstract: OBJECTIVE
  Transtympanic administration of gentamicin is effective for treating patients with intractable vertigo. This study explored the spatial and temporal distribution of gentamicin in vestibular end-organs after transtympanic administration.
  
  
  METHODS
  Thirty guinea pigs were transtympanically injected with gentamicin conjugated to Texas Red (GTTR) and their vestibular end-organs examined after various survival periods. Another 9 guinea pigs received GTTR at different doses. Nine animals received Texas Red only and served as controls. We used confocal microscopy to determine the cellular distribution of GTTR in semicircular canal cristae, as well as the utricular and saccular maculae.
  
  
  RESULTS
  The most intense GTTR labeling was present in the saccule compared to other vestibular end-organs. GTTR fluorescence was detected predominantly in type I hair cells, type II hair cells and transitional cells after a single transtympanic dose of GTTR (0.1 mg/ml, 0.05 ml), while only weak fluorescence was observed in non-sensory cells such as supporting cells, dark cells and lumenal epithelial cells. Transitional cells displayed intense GTTR fluorescence in the supra-nuclear regions 24 h after transtympanic injection that was retained for at least 4 weeks. A decreasing spatial gradient of GTTR fluorescence was observed sensory epithelial regions containing central type I to peripheral type I and then type II hair cells in the crista ampullaris, and from striolar to extra-striolar hair cells within the vestibular macula. GTTR fluorescence extended from being restricted to the apical cytoplasm at lower doses to the entire cell body of type I hair cells with increasing dose. GTTR fluorescence reached peak intensities for individual regions of interest within the cristae and maculae between 3 and 7 days after transtympanic injection.
  
  
  CONCLUSIONS
  The saccular uptake of GTTR is greater than other vestibular end-organs after transtympanic injection in the semicircular canals.
authors: Department of Otology and Skull Base Surgery, Eye Ear Nose and Throat Hospital, Fudan University, 83 Fen Yang Road, Shanghai 200031, China.
authors: Ru
authors: R
authors: Zhang
authors: Yi-Bo
authors: YB
authors: Zhang
authors: Chun-Fu
authors: CF
authors: Dai
authors: Peter S
authors: PS
authors: Steyger
mesh_terms: D008267:Acoustic Maculae / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000378:metabolism*; D005839:Gentamicins / Q000008:administration & dosage* / Q000378:metabolism*; D006168:Guinea Pigs; D007267:Injections; D008297:Male; D018613:Microscopy, Confocal; D054776:Semicircular Ducts / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014432:Tympanic Membrane; D014722:Vestibule, Labyrinth / Q000378:metabolism*; D014966:Xanthenes / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D005839:Gentamicins; D014966:Xanthenes; C034657:Texas red
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