Abstract
Cochlear implants electrically stimulate spiral ganglion neurons (SGNs) in order to provide speech cues to severe-profoundly deaf patients. In normal hearing cochleae the SGNs depend on endogenous neurotrophins secreted by sensory cells in the organ of Corti for survival. SGNs gradually degenerate following deafness and consequently there is considerable interest in developing clinically relevant strategies to provide exogenous neurotrophins to preserve SGN survival. The present study investigated the safety and efficacy of a drug delivery system for the cochlea using nanoengineered silica supraparticles. In the present study we delivered Brain-derived neurotrophic factor (BDNF) over a period of four weeks and evaluated SGN survival as a measure of efficacy. Supraparticles were bilaterally implanted into the basal turn of cochleae in profoundly deafened guinea pigs. One ear received BDNF-loaded supraparticles and the other ear control (unloaded) supraparticles. After one month of treatment the cochleae were examined histologically. There was significantly greater survival of SGNs in cochleae that received BDNF supraparticles compared to the contralateral control cochleae (repeated measures ANOVA, p = 0.009). SGN survival was observed over a wide extent of the cochlea. The supraparticles were well tolerated within the cochlea with a tissue response that was localised to the site of implantation in the cochlear base. Although mild, the tissue response was significantly greater in cochleae treated with BDNF supraparticles compared to the controls (repeated measures ANOVA, p = 0.003). These data support the clinical potential of this technology particularly as the supraparticles can be loaded with a variety of therapeutic drugs.
Highlights
Hearing loss is one of the most common sensory deficits affecting over 5.3% of people worldwide
A primary cause of spiral ganglion neurons (SGNs) degeneration is the loss of the endogenous supply of neurotrophins, in particular BrainDerived Neurotrophic Factor (BDNF) and Neurotrophin 3 (NT-3), which are normally produced by hair cells and supporting cells in the organ of Corti [8,9,10,11,12,13]
There is a clear difference in SGN survival with the cochleae that received BDNF-SP exhibiting more SGNs compared to the contralateral cochleae that received Control-SP
Summary
Hearing loss is one of the most common sensory deficits affecting over 5.3% of people worldwide (approximately 360 million people: World Health Organization, 2012). A primary cause of SGN degeneration is the loss of the endogenous supply of neurotrophins, in particular BrainDerived Neurotrophic Factor (BDNF) and Neurotrophin 3 (NT-3), which are normally produced by hair cells and supporting cells in the organ of Corti [8,9,10,11,12,13]. Both BDNF and NT-3 are required for normal neural development and innervation of cochlear hair cells with NT-3 important for synaptogenesis [14, 15]. Clinically relevant strategies that can prevent the progressive degeneration of SGN with cochlear implantation have received substantial interest
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
