In vivo adenoviral transduction of the neonatal rat cochlea and middle ear

Virally mediated gene transfer to the adult mammalian ear appears to be a p owerful strategy to investigate gene function in the auditory system and to develop new therapeutic treatment for hearing impaired patients. However, there has been little work done in the neonatal middle and inner ear. In th is study, a recombinant adenoviral (AdV) vector was used for gene transfer of a beta -galactosidase (beta -gal) reporter gene to the neonatal middle e ar and cochlea of 5 day old rats. For transduction of middle ear, AdV was i njected through the tympanic membrane into the tympanic cavity. Three and 7 days later, strong expression of P-gal was observed in epithelial cells of the mucosal but not in the underlying stroma or mesenchyme. There was litt le or no infiltration of leukocytes. No expression of P-gal was detected in side the cochlea or vestibular system. When AdV was injected into the basal turn of the cochlea, high levels of P-gal expression were observed in cell s lining the perilymphatic space and in parts of the spiral ligament 3, 7 a nd 21 days later. Spiral ganglion cells did not express P-gal. However, vir ally mediated gene transfer was observed in some cells of the organ of Cort i. A moderate infiltration of leukocytes into the labyrinth was observed, b ut no vestibular or auditory dysfunction. These results demonstrate that ne onatal middle ear and cochlear cells can be successfully transduced with an AdV vector in vivo, without obvious morphological signs of inflammation or cellular damage. AdV vectors provide a tool for investigation of the role of genes in influencing the development of middle and inner ear structures. Virally mediated expression of protective genes could also be used to resc ue hair cells or spiral ganglion cells from congenital degeneration or dama ge. (C) 2001 Elsevier Science B.V. All rights reserved.