Delivery of Channel Rhodopsin for Optogenetic Control of Neurons in the Cochlea

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): The cochlear implant (CI) provides meaningful sound and speech perception to the majority of patients with severe to profound sensorineural hearing loss. The CI electrode bypasses the defective or absent hair cells of the deaf inner ear to electrically stimulate the spiral ganglion cells (SGCs), the first order neurons of the auditory system. Although most CI users receive auditory benefits, outcomes vary widely across similar subjects. In addition, a number of patients do not have open set word recognition scores that exceed 50% and virtually all CI patients report difficulty in noisy environments and musical appreciation. One explanation may be that the electrical stimulation paradigm used by current systems sets fundamental limits on auditory performance. Specifically, although speech perception has been shown to increase with the number of electrodes, the number of effective channels is diminished by the longitudinal spread of electricity. This results in channel cross-tal and the activation of neuronal populations remote from the site of the electrode. In order to address these limitations of current implant technology, we will use an exciting new approach called optogenetics to stimulate neurons of the inner ear with light. Light offers a key advantage over electricity because it can be focused and allows, in theory, the selective activation of hundreds of independent acoustic channels. Channelrhodopsin-2 (ChR2) is a light-sensitive protein that can be delivered into neurons using a viral vector and has been used successfully in many systems, including the CNS and in the visual pathways. Optogenetic control of auditory pathways through transduction of SGCs has not yet been reported. Our hypothesis is that modification of inner ear neurons using direct viral vector transduction or stem cell-mediated transfer of ChR2 in vivo is feasible and that ChR2-expressing neurons are capable of generating an optically-evoked auditory response. We propose that photosensitization of SGCs and insertion of an optical electrode for controlled stimulation of the inner ear may provide the basis for future CI technology based on light.