Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons.
Spiral ganglion neurons often degenerate in the deaf ear, compromising the function of cochlear implants. Cochlear implant function can be improved by good preservation of the spiral ganglion neurons, which are the target of electrical stimulation by the implant. Brain derived neurotrophic factor (BDNF) has previously been shown to enhance spiral ganglion survival in experimentally deafened ears. Providing enhanced levels of BDNF in human ears may be accomplished by one of several different methods. The goal of these experiments was to test a modified design of the cochlear implant electrode that includes a coating of fibroblast cells transduced by a viral vector with a BDNF gene insert. To accomplish this type of ex vivo gene transfer, we transduced guinea pig fibroblasts with an adenovirus with a BDNF gene cassette insert, and determined that these cells secreted BDNF. We then attached BDNF-secreting cells to the cochlear implant electrode via an agarose gel, and implanted the electrode in the scala tympani. We determined that the BDNF expressing electrodes were able to preserve significantly more spiral ganglion neurons in the basal turns of the cochlea after 48 days of implantation when compared to control electrodes. This protective effect decreased in the higher cochlear turns. The data demonstrate the feasibility of combining cochlear implant therapy with ex vivo gene transfer for enhancing spiral ganglion neuron survival.
Rejali
Darius
D
Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, USA, and University Hospitals Warwickshire and Coventry NHS Trust, Coventry CV2 2DX, UK.
Lee
Valerie A
VA
Abrashkin
Karen A
KA
Humayun
Nousheen
N
Swiderski
Donald L
DL
Raphael
Yehoash
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D019929:Cochlear Implantation; D003054:Cochlear Implants; D003638:Deafness / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D004195:Disease Models, Animal; D004976:Ethacrynic Acid; D005240:Feasibility Studies; D005347:Fibroblasts / Q000378:metabolism; D015316:Genetic Therapy / Q000295:instrumentation* / Q000379:methods; D005822:Genetic Vectors; D006168:Guinea Pigs; D007612:Kanamycin; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000378:metabolism; D011474:Prosthesis Design; D012685:Sepharose / Q000378:metabolism; D013136:Spiral Ganglion / Q000378:metabolism* / Q000473:pathology; D014161:Transduction, Genetic
D019208:Brain-Derived Neurotrophic Factor; D007612:Kanamycin; D012685:Sepharose; D004976:Ethacrynic Acid