According to a report of the WHO, approximately 466 million people – 5% of the world’s population – suffer from disabling hearing impairment, commonly causing social isolation, depression, and reduction in professional capabilities. Therefore, understanding how hearing works and combating hearing impairment is of great importance. So far, despite major research efforts a causal treatment based on pharmacology, gene therapy, or stem cells is not yet available for its most common form: sensorineural hearing impairment. Hearing aids and/or cochlear implants (CIs) represent the state-of-the-art approaches for partial restoration of auditory function and are likely to remain key means for alleviating sensorineural hearing impairment also during the coming decades.
CIs bypass cochlear dysfunction via direct electric stimulation of auditory neurons of the inner ear and are considered the most successful neuroprosthesis, used in more than 700,000 hearing impaired patients worldwide. Cis enable open speech comprehension in most users and have become a major tool in auditory research. However, the use of current Cis has limitations arising from the wide spread of current around each electrode contact which leads to channel-crosstalk and limits the number of useful frequency channels to typically less than ten in clinical CIs. Since the coding of sound frequency in the inner ear is tied to the location of the excited neuron and thus to the spatial spread of excitation within the ear, users of electrical Cis suffer from poor frequency resolution of hearing and therefore show poor comprehension of speech in noisy environments and typically cannot follow musical melodies. The low frequency resolution limits the use of electric CIs in basic research, too. Increasing the frequency and intensity resolution of auditory coding is a central objective for improving the CI.
Optical stimulation of auditory neurons, which we established in the project “OptoHear”, is a novel approach that promises a dramatic increase of the frequency resolution of CIs, since light can be more easily confined in the cochlea and therefore less spread of excitation than in electrical implants can be achieved (Fig. 1). The increased frequency resolution provides unprecedented opportunities for auditory research and promises to overcome the major bottleneck of current CIs.
The application of optogenetics to the cochlea, pioneered by our research team, uses virus-mediated expression of Channelrhodopsins, light-gated ion channels that can be used to activate neurons, to render neurons sensitive to light. This method, coined “optogenetics” has revolutionized the life sciences and is in rapid development with various applications and advances such as the engineering of improved Channelrhodopsin variants and vectors, some of which also serve as vectors in clinical trials on gene therapy. Important technological advances enable tailored optical stimulation. Thin-film light emitting diodes (LEDs) reach high power efficiency, can be miniaturized (µLEDs) and prepared for shaping the beam of the emitted light. Flexible waveguide arrays, as well as thin-film flexible electronics on polymer substrates have become available.
“OptoHear” has established and used cochlear optogenetics as a research tool, validated its potential for research and hearing restoration, and prepared translation into the clinic by validating the safety and efficiency of auditory optogenetics in rodents. Further experiments in marmoset monkeys as a last step before first clinical trials are underway, which we hope to achieve starting 2026.
