Abstract
The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the residual spiral ganglion neurons. These neurons, however, undergo progressive degeneration after hearing loss, marked initially by peripheral fibre retraction and ultimately culminating in cell death. This research aims to use gene therapy techniques to both hold and reverse this degeneration by providing a sustained and localised source of neurotrophins to the deafened cochlea. Adenoviral vectors containing green fluorescent protein, with or without neurotrophin-3 and brain derived neurotrophic factor, were injected into the lower basal turn of scala media of guinea pigs ototoxically deafened one week prior to intervention. This single injection resulted in localised and sustained gene expression, principally in the supporting cells within the organ of Corti. Guinea pigs treated with adenoviral neurotrophin-gene therapy had greater neuronal survival compared to contralateral non-treated cochleae when examined at 7 and 11 weeks post injection. Moreover; there was evidence of directed peripheral fibre regrowth towards cells expressing neurotrophin genes after both treatment periods. These data suggest that neurotrophin-gene therapy can provide sustained protection of spiral ganglion neurons and peripheral fibres after hearing loss.
Highlights
Hearing loss is the most common sensory deficit in developed countries, with an estimated 278 million people globally suffering from a disabling hearing impairment [1,2]
Post hoc analysis showed a statistical difference between the normal hearing animals and all other time points post deafening, there was a significant difference between one and eight weeks post deafening
The key finding of this study is that NT gene therapy provides effective and sustained neural protection in the long term deafened cochlea
Summary
Hearing loss is the most common sensory deficit in developed countries, with an estimated 278 million people globally suffering from a disabling hearing impairment [1,2]. This number is predicted to rise as the population ages. The loss of HCs and supporting cells results in an ongoing degeneration of SGNs [4,5,6,7,8,9,10], reducing the number of SGNs available for stimulation by a CI. Neurotrophins (NTs), in particular neutrophin-3 (NT3) and brain derived neurotrophic factor (BDNF), have been shown to play key roles in both the development and survival of SGNs [11,12,13,14,15,16], and as such have been the focus of research aiming to mitigate degeneration of SGNs after deafness
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