Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity

Gentamicin administration often results in cochlear and/or vestibular hair cell loss and hearing and balance impairment. It has been demonstrated that adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) can protect cochlear hair cells against ototoxic injury. In this study, we evaluated the protective effects of adenovirus-mediated over expression of GDNF against gentamicin ototoxicity An adenovirus vector expr essing the human GDNF gene (Ad.GDNF) was administered into the scala vestib uli as a rescue agent at the same time as gentamicin, or as a protective ag ent, 7 days before gentamicin administration. Animals in the Rescue group d isplayed hearing thresholds that were significantly better than those measu red in the Gentamicin or Ad.LacZ/Gentamicin groups. In the Protection group , AdGDNF afforded significant preservation of utricular hair cells. The dat a demonstrated protection of the inner ear structure, and rescue of the inn er ear structure and function against ototoxic insults. These experiments s uggest that inner ear gene therapy may be developed as a clinical tool for protecting the ear against environmentally induced insults.