Obiettivo
Disabling hearing impairment (HI) affects 360 million people worldwide and prevalence increases with age. So far, no causal treatment is available for its most common form, sensorineural HI. I propose to establish, characterize, and employ optogenetic stimulation of the cochlea, which provides unprecedented opportunities for auditory research and promises a fundamental advance of hearing restoration.
Sound is encoded by spiral ganglion neurons (SGNs) with high frequency-, intensity-, and time-resolution. Hearing can be enabled via electric stimulation of SGNs, which is employed in current hearing restoration with cochlear implants (CIs) and also used in auditory research. CIs enable speech comprehension in most users, but the quality of ‘electric hearing’ is low, with poor frequency resolution.
The goal of OptoHear is to overcome this fundamental limitation by increasing the number of independent coding channels via spatially confined optical stimulation of channelrhodopsin (ChR)-expressing SGNs by tens of light emitters along the cochlear axis (cochlear optogenetics). This promises a dramatic improvement in the frequency resolution of artificial sound coding. As proof of principle, we achieved virus-mediated expression of ChR in SGNs, recorded light-evoked auditory activity and demonstrated improved frequency resolution for optical vs. electric stimulation in rodents. We co-developed and implanted optical multichannel CIs and studied their position in the rodent cochlea using X-ray tomography.
We will optimize the expression of best-suited ChRs in SGNs, establish multichannel optical stimulation, characterize neuronal responses to cochlear optogenetics along the auditory pathway by physiological and behavioural approaches, and employ cochlear optogenetics for fundamental auditory research. OptoHear will establish and use cochlear optogenetics as a research tool, validate its potential for research and hearing restoration, and prepare translation into the clinic.
Campo scientifico
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesmedical biotechnologyimplants
- medical and health sciencesbasic medicinepharmacology and pharmacy
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
37075 Goettingen
Germania