Blindness affects millions of people worldwide and has devastating consequences for those affected. It is often caused by a loss of photoreceptors in the retina, whose residual cellular network remains largely unaffected. Various strategies have been chosen to restore vision, such as electrical stimulation with retinal implants. More recently, natural photoreceptor proteins and stem cells have been explored. We propose a radically different ¿photopharmacological¿ approach toward vision restoration that is based on synthetic photoswitches. These are combined in various ways with natural receptor proteins to create hybrid photoreceptors, which can then sensitize neurons toward light. In a way we are ¿teaching old receptors new tricks¿ and let them carry out functions that they have not evolved for in Nature. Our hybrid photoreceptors and photochromic drugs work well in experimental animals and have already been shown to influence their visual behavior. To make these molecules work in humans, we need to improve their photophysical properties and investigate their delivery, stability and pharmacology. This requires an extensive program in synthetic chemistry, which should be accompanied by effective and immediate neurobiological evaluation. Our very general approach to optically controlling neural activity can be applied to other functions and malfunctions of the nervous system, such as pain or epilepsy, but its greatest medical potential currently lies in the restoration of vision.
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