Restoring light sensitivity using tunable near-infrared sensors

• Published in: Science (American Association for the Advancement of Science) 2020-06, Vol.368 (6495), p.1108-1113
• Main Authors: Nelidova, Dasha, Morikawa, Rei K., Cowan, Cameron S., Raics, Zoltan, Goldblum, David, Scholl, Hendrik P. N., Szikra, Tamas, Szabo, Arnold, Hillier, Daniel, Roska, Botond
• Format: Article
• Language: English
• Subjects: Antibodies; Blindness; Cell activation; Climate; Cones; Degeneration; Gold; I.R. radiation; Infrared detectors; Ion channels; Light; Nanorods; Neurons; Photoreception; Photoreceptors; Recovery of function; Retina; Retinal degeneration; Sensitivity; Sensors; Temperature; Transient receptor potential proteins; Visual cortex; Visual perception; Visual stimuli; Wavelengths
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaz5887

Photoreceptor degeneration is an important cause of blindness. Nelidova et al. used tunable, near-infrared sensors to render diseased photoreceptors light sensitive again (see the Perspective by Franke and Vlasits). Gold nanorods capable of detecting infrared light were coupled with an antibody to temperature-sensitive ion channels. When the nanorods absorbed light and converted it into heat, the coupled ion channels were gated by infrared light. In a mouse model of retinal degeneration, these ion channels were successfully targeted to cone photoreceptors, and responses to near infrared light could be detected. In the primary visual cortex, more cells responded to near-infrared stimuli in mice expressing these ion channels than in controls. By changing the length of the gold nanorods, the system could be tuned to different infrared wavelengths. Science , this issue p. 1108 ; see also p. 1057 An experimental strategy aims to restore visual responses after retinal degeneration. Enabling near-infrared light sensitivity in a blind human retina may supplement or restore visual function in patients with regional retinal degeneration. We induced near-infrared light sensitivity using gold nanorods bound to temperature-sensitive engineered transient receptor potential (TRP) channels. We expressed mammalian or snake TRP channels in light-insensitive retinal cones in a mouse model of retinal degeneration. Near-infrared stimulation increased activity in cones, ganglion cell layer neurons, and cortical neurons, and enabled mice to perform a learned light-driven behavior. We tuned responses to different wavelengths, by using nanorods of different lengths, and to different radiant powers, by using engineered channels with different temperature thresholds. We targeted TRP channels to human retinas, which allowed the postmortem activation of different cell types by near-infrared light.