Cochlear gene transfer: round window versus cochleostomy inoculation.

Two possible approaches for cochlear gene transfer have been inoculation via the round window membrane and through a cochleostomy. The aim of this study was to determine which of the two is more effective. Using both approaches, normal-hearing and deafened guinea pigs were inoculated with adenovirus carrying the reporter gene lacZ. After 5 days, the animals were killed and the cochlear tissue was stained with X-gal. The distribution and intensity of staining was estimated by a score system developed to compare gene transfer results between animals. We found that gene transfer via the cochleostomy resulted in a better distribution throughout the cochlea and in higher staining intensity, due to more efficient transfection. Auditory brainstem response (ABR) results showed that neither virus inoculation through a cochleostomy nor through the round window membrane had a significant effect on the click-ABR threshold measured on day 5 following virus injection. Gene transfer via both approaches was also found to be more effective in deafened animals than in hearing animals.