Therapy of impairment of guinea pig's spiral ganglion cells by adenovirus-mediated human neurotrophin 3 gene

Objective To observe the adenovirus-mediated NT-3 gene expression in guinea pig's cochlea,and to evaluate the protective effect of NT-3 gene therapy to kainic acid(KA) induced excitotoxic damage of the spiral ganglion cells.Methods Twenty healthy guinea pigs were randomly divided into three groups.In the first group(6 animals,Ad-NT3 group),perilymphatic perfusion of KA((4 mmol/L),10 μl) into the right scala tympani was performed for animal model of excitotoxic cochlear impairment.The complex of adenovirus vectors and human NT-3 gene(pAdeasy-NT3) was delivered into right perilymphatic space 7 days after KA treatment.For the second group(7 animals,KA group),KA(4 mmol/L,10 μl) was injected into the right scala tympani as experimental control.The third group(7 animals,blank group) were utilized as blank control;perilymphatic perfusion wasn't performed.All the animals of Ad-NT3 group and KA group were sacrificed 20 days after KA perfusion for morphological observation of type Ⅰ spiral ganglion cells and NT-3 immunoreactivity.The animals in blank group were sacrificed after an equivalent survival period.Results Thirty days after the perfusion of pAdeasy-NT3,cochlear NT-3 immunoreactivity was observed in the Ad-NT3 group,which was significantly stronger than that in the KA group.The number of degenerated spiral ganglion cells in the Ad-NT3 group was significantly lower than that in the KA group(P(0.001)).Conclusion ① Adenovirus-mediated human NT-3 gene(pAdeasy-NT3) can be expressed at high level in guinea pig cochlea.Even though administered 7 days after KA treatment,it may prevent spiral ganglion cells from being damaged by the excitotoxicity of KA.② There is a precious cure opportunity for inner ear gene therapy before the irreversible impairment of cochlear ganglion cells.