Unblinding with infrared nanosensors

doi:10.1126/science.abc2294

GSTDTAP > 气候变化

DOI	10.1126/science.abc2294
	Unblinding with infrared nanosensors
	Katrin Franke; Anna Vlasits
	2020-06-05
发表期刊	Science
出版年	2020
英文摘要	Many cases of blindness result from progressive loss of photoreceptors, which are the light-sensing cells in the eye. For individuals with such progressive blindness, potential therapies aim at restoring vision by making the retina light-sensitive again while minimally interfering with any healthy photoreceptors—goals that are usually contradictory. Many current therapeutic strategies interfere with remaining vision, making them primarily suitable for patients who have lost all light sensitivity. On page 1108 of this issue, Nelidova et al. ([ 1 ][1]) present a potential solution to this conundrum: making the retina sensitive to infrared light, which is largely undetectable by human photoreceptors. They use engineered nanoparticle sensors and gene therapy to induce infrared light sensitivity in mice with inherited degenerative blindness and in postmortem human retinas. This approach might avoid damage to functional photoreceptors by preventing saturation or hyperactivation while inducing light sensitivity in patients with partial retinal degeneration. At the level of the retina, a multilayered array of more than 100 types of neurons sorts complex visual features, such as motion and color, into separate channels to send to the brain ([ 2 ][2]). When photoreceptors fail, the entire downstream network is affected, and restoring the visual system's physiological function becomes challenging. In addition, mammalian rod and cone photoreceptors, unlike those of some species in the animal kingdom, cannot regenerate. For patients with degenerative blindness, the aim of therapy is therefore twofold: to slow degeneration while preserving remaining vision, and to restore some vision once degeneration is complete. Several types of therapies show promise in slowing degenerative blindness, including targeted gene therapies and stem cell–based approaches ([ 3 ][3], [ 4 ][4]). One example is Leber congenital amaurosis, a disease for which a gene therapy has led to an improvement in patients' visual function ([ 5 ][5]). Other therapeutic strategies include electrical implants and optogenetic gene therapies, which aim at restoring vision ([ 4 ][4], [ 6 ][6]). The optogenetic approach induces the expression of light-sensitive ion channels through gene therapy to restore light sensitivity to retinal neurons. Several molecular candidates can restore light sensitivity in animals and in postmortem human retinas ([ 7 ][7]), and some are now in clinical trials. But currently these molecules require much more light than normal photoreceptors to become activated, and most therapies would require video goggles to boost the effective brightness of incoming images. For patients with some remaining vision, this strategy would saturate or possibly even damage their remaining functional photoreceptors. Nelidova et al. circumvent these problems by making the retina sensitive to infrared light, which is light beyond the visible spectrum and emitted by, for example, warm objects. Their approach combines gene therapy with the use of gold nanorods, an emerging nanotechnology for activating molecules in the human body ([ 8 ][8]). Nelidova et al. use gold nanorods as antennae for infrared light, transforming the light into heat through a process called surface plasmon resonance. Genetic constructs injected into the eye then cause the expression of temperature-sensitive transient receptor potential (TRP) channels in photoreceptors. Such TRP channels are normally found in mammalian heat-sensing nerves in the skin, as well as in the infrared-sensing organs of some snakes and vampire bats, and are able to transform heat into electrical changes in the membranes of cells ([ 9 ][9]). The authors use antibodies to link the heat-emitting gold nanorods to heat-sensitive TRP channels. Thus, infrared light can activate photoreceptors (see the figure). To test whether this strategy can restore visual function, Nelidova et al. express TRP channels in cone photoreceptors of a mouse model of degenerative blindness. They find that neural activity measured in the retina and visual cortex correlated with infrared light stimuli. In addition, they show that treated blind mice can use their infrared light sensitivity to learn a simple visually guided behavior. The authors tested their nanorod–TRP channel approach in cultured, light-insensitive postmortem human retinas, demonstrating that it introduces infrared light sensitivity to this tissue—a critical step in evaluating its relevance for human patients. A different nanotechnology, called up-conversion nanoparticles, which binds to photoreceptors and “up-converts” infrared into visible light, can make photoreceptors virtually infrared-sensitive ([ 10 ][10]). Although degenerating photoreceptors would likely not be able to use up-conversion nanoparticles, mice treated with this technology used their infrared sensitivity to perform complex visual tasks including shape recognition. Such detailed behavioral evaluation is critical, because it is not clear to what extent the already-developed brain can interpret a new sensory modality to guide behavior—although studies support some plasticity of the adult mammalian brain for integrating new sensory input ([ 11 ][11], [ 12 ][12]). Both examples demonstrate the strengths of nanotechnology tools over other methods. These tools are more light-sensitive than conventional optogenetics, approaching the sensitivity needed to work under normal daylight levels. Because the nanoparticles harness a different wavelength of light, it might be possible for normal vision and infrared vision to operate in parallel. ![Figure][13] Nanorods and heat-sensing proteins for infrared detection Injecting the eye with infrared-sensitive nanorods and genetic constructs to induce the expression of temperature-sensitive transient receptor potential (TRP) channels in photoreceptors may confer infrared vision. GRAPHIC: N. CARY/ SCIENCE The nanorod–TRP channel approach used by Nelidova et al. faces further challenges before it can reach the clinic. It is promising that gold nanorods have, so far, appeared to be safe in humans ([ 13 ][14]). Similarly, ocular gene therapies seem to be low-risk and effective ([ 3 ][3], [ 4 ][4]). However, the main challenge of any ocular gene therapy is to improve the efficiency and completeness of gene introduction ([ 3 ][3]) as well as to provide long-term effectiveness ([ 14 ][15]). More specifically, because nanorods and TRP channels cannot currently be targeted selectively to degenerating photoreceptors, the interaction between induced infrared sensitivity and the intrinsic light sensitivity of healthy photoreceptors requires further investigation. In addition, many objects that humans see are not necessarily infrared-emitting or infrared-reflecting; thus, goggles to convert visible light to infrared light would likely be necessary. Nonetheless, this system has exceptional promise for basic research. Tools that can reintroduce light sensitivity to postmortem human retinas ([ 15 ][16]) offer the potential for studying human retinal function in much greater detail than was previously possible. 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领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/273432
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Katrin Franke,Anna Vlasits. Unblinding with infrared nanosensors[J]. Science,2020.
APA	Katrin Franke,&Anna Vlasits.(2020).Unblinding with infrared nanosensors.Science.
MLA	Katrin Franke,et al."Unblinding with infrared nanosensors".Science (2020).