Toward Optogenetic Hearing Restoration.

The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in the majority of the million otherwise deaf patients. In hearing by electrical stimulation of the auditory nerve, the broad spread of current from each electrode acts as a bottleneck that limits the transfer of sound frequency information. Hence, there remains a major unmet medical need for improving the quality of hearing with CIs. Recently, optogenetic stimulation of the cochlea has been suggested as an alternative approach for hearing restoration. Cochlear optogenetics promises to transfer more sound frequency information, hence improving hearing, as light can conveniently be confined in space to activate the auditory nerve within smaller tonotopic ranges. In this review, we discuss the latest experimental and technological developments of optogenetic hearing restoration and outline remaining challenges en route to clinical translation.

Genome engineering of a neuronal specific, optogenetic, induced pluripotent stem cell line.

Control of neuronal activity by optogenetic tools is increasingly explored in disease modelling and optogenetics and holds great promise for regenerative therapy. To investigate neuronal connectivity with other excitable cells we established an optogenetic induced pluripotent stem cell line. The SynfChrimson line harbors a stably integrated, fast, red light-activatable channel (f-Chrimson), under the control of synapsin promotor in the AAVS1 locus. Multielectrode array analysis showed that SynfChrimson derived neurons are light-activatable. The specificity of the SynfChrimson function in neurons was validated by cardiomyocyte differentiations which do not respond to light stimulations.