Restoring light sensitivity using tunable near-infrared sensors

Science ◽  
2020 ◽  
Vol 368 (6495) ◽  
pp. 1108-1113 ◽  
Author(s):  
Dasha Nelidova ◽  
Rei K. Morikawa ◽  
Cameron S. Cowan ◽  
Zoltan Raics ◽  
David Goldblum ◽  
...  

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.

Nanoscale ◽  
2022 ◽  
Author(s):  
Wei-Hsu Chen ◽  
Taiki Onoe ◽  
Masao Kamimura

In this study, we developed a novel biodegradable/photothermal polymer micelle-based remote-activation method for a temperature-sensitive ion channel, namely transient receptor potential cation channel subfamily V member 1 (TRPV1). Biodegradable/photothermal polymer...


2007 ◽  
Vol 292 (1) ◽  
pp. R37-R46 ◽  
Author(s):  
Andrej A. Romanovsky

While summarizing the current understanding of how body temperature (Tb) is regulated, this review discusses the recent progress in the following areas: central and peripheral thermosensitivity and temperature-activated transient receptor potential (TRP) channels; afferent neuronal pathways from peripheral thermosensors; and efferent thermoeffector pathways. It is proposed that activation of temperature-sensitive TRP channels is a mechanism of peripheral thermosensitivity. Special attention is paid to the functional architecture of the thermoregulatory system. The notion that deep Tb is regulated by a unified system with a single controller is rejected. It is proposed that Tb is regulated by independent thermoeffector loops, each having its own afferent and efferent branches. The activity of each thermoeffector is triggered by a unique combination of shell and core Tbs. Temperature-dependent phase transitions in thermosensory neurons cause sequential activation of all neurons of the corresponding thermoeffector loop and eventually a thermoeffector response. No computation of an integrated Tb or its comparison with an obvious or hidden set point of a unified system is necessary. Coordination between thermoeffectors is achieved through their common controlled variable, Tb. The described model incorporates Kobayashi’s views, but Kobayashi’s proposal to eliminate the term sensor is rejected. A case against the term set point is also made. Because this term is historically associated with a unified control system, it is more misleading than informative. The term balance point is proposed to designate the regulated level of Tb and to attract attention to the multiple feedback, feedforward, and open-loop components that contribute to thermal balance.


2017 ◽  
Vol 149 (4) ◽  
pp. 455-464 ◽  
Author(s):  
Paulus Saari ◽  
Andrew S. French ◽  
Päivi H. Torkkeli ◽  
Hongxia Liu ◽  
Esa-Ville Immonen ◽  
...  

Electrophysiological studies in Drosophila melanogaster and Periplaneta americana have found that the receptor current in their microvillar photoreceptors is generated by two light-activated cationic channels, TRP (transient receptor potential) and TRPL (TRP-like), each having distinct properties. However, the relative contribution of the two channel types to sensory information coding by photoreceptors remains unclear. We recently showed that, in contrast to the diurnal Drosophila in which TRP is the principal phototransduction channel, photoreceptors of the nocturnal P. americana strongly depend on TRPL. Here, we perform a functional analysis, using patch-clamp and intracellular recordings, of P. americana photoreceptors after RNA interference to knock down TRP (TRPkd) and TRPL (TRPLkd). Several functional properties were changed in both knockdown phenotypes: cell membrane capacitance was reduced 1.7-fold, light sensitivity was greatly reduced, and amplitudes of sustained light-induced currents and voltage responses decreased more than twofold over the entire range of light intensities. The information rate (IR) was tested using a Gaussian white-noise modulated light stimulus and was lower in TRPkd photoreceptors (28 ± 21 bits/s) than in controls (52 ± 13 bits/s) because of high levels of bump noise. In contrast, although signal amplitudes were smaller than in controls, the mean IR of TRPLkd photoreceptors was unchanged at 54 ± 29 bits/s1 because of proportionally lower noise. We conclude that TRPL channels provide high-gain/high-noise transduction, suitable for vision in dim light, whereas transduction by TRP channels is relatively low-gain/low-noise and allows better information transfer in bright light.


2013 ◽  
Vol 6 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Gehoon Chung ◽  
Seog Bae Oh

Despite the high incidence of dental pain, the mechanism underlying its generation is mostly unknown. Functional expression of temperature-sensitive transient receptor potential (thermo-TRP) channels, such as TRPV1, TRPV2, TRPM8, and TRPA1 in dental primary afferent neurons and TRPV1, TRPV2, TRPV3, TRPV4, and TRPM3 in odontoblasts, has been demonstrated and suggested as responsible for dental pain elicited by hot and cold food. However, dental pain induced by light touch or sweet substance cannot be explained by the role of thermo-TRP channels. Most of current therapeutics of dentin hypersensitivity is based on hydrodynamic theory, which argues that light stimuli such as air puff and temperature changes cause fluid movement within dentinal tubule, which is then transduced as pain. To test this theory, various TRP channels as candidates of cellular mechanotransducers were studied for expression in dental primary afferents and odontoblasts. The expression of TRPV1, TRPV2, TRPA1, TRPV4, and TRPM3 in trigeminal neurons and TRPV1, TRPV2, TRPV3, TRPV4 and TRPM3 in odontoblasts has been revealed. However, their roles as cellular mechanotransducers are controversial and contribution to generation of dental pain is still elusive. This review discusses recent advances in understanding of molecular mechanism underlying development of dental pain.


2020 ◽  
Vol 16 (9) ◽  
pp. 1381-1393
Author(s):  
Yuan Peng ◽  
Zhenwei Su ◽  
Xin Wang ◽  
Teng Wu ◽  
Hong Xiao ◽  
...  

Chemotherapy of hepatocellular carcinoma (HCC) is facing drug resistance, which leads to unsatisfactory therapeutic effect. Thus, a combination therapy using multiple drugs may overcome this challenge. The current study aims to realize a synergistic chemotherapy of HCC by using a near-infrared light (NIR) responsive nanocarrier to co-deliver the chemotherapeutic drug Doxorubicin (DOX) and molecular targeting agent Sorafenib (SF). The nanocarrier, which could effectively load DOX in its aqueous core while SF and IR-780 in its lipid bilayer, is fabricated from a temperature-sensitive liposome (TSL) modified with PF127. An efficient SF and DOX co-loading was achieved, and meanwhile the effective photothermal conversion of IR-780 under NIR laser may cause a disassembly of the liposome structure which may trigger a rapid drug release in tumor site, greatly boosting the synergetic chemotherapeutic effect. The NIR laser-triggered drug release and the synergistic anti-tumor effect were evaluated both in cell and animal experiments, which revealed that the PF127-modified TSL is a potent nanoplatform to improve the HCC treatment through co-delivering a drug combination.


2011 ◽  
Vol 300 (6) ◽  
pp. R1278-R1287 ◽  
Author(s):  
Daniel D. McCoy ◽  
Wendy M. Knowlton ◽  
David D. McKemy

The proper detection of environmental temperatures is essential for the optimal growth and survival of organisms of all shapes and phyla, yet only recently have the molecular mechanisms for temperature sensing been elucidated. The discovery of temperature-sensitive ion channels of the transient receptor potential (TRP) superfamily has been pivotal in explaining how temperatures are sensed in vivo, and here we will focus on the lone member of this cohort, TRPM8, which has been unequivocally shown to be cold sensitive. TRPM8 is expressed in somatosensory neurons that innervate peripheral tissues such as the skin and oral cavity, and recent genetic evidence has shown it to be the principal transducer of cool and cold stimuli. It is remarkable that this one channel, unlike other thermosensitive TRP channels, is associated with both innocuous and noxious temperature transduction, as well as cold hypersensitivity during injury and, paradoxically, cold-mediated analgesia. With ongoing research, the field is getting closer to answering a number of fundamental questions regarding this channel, including the cellular mechanisms of TRPM8 modulation, the molecular context of TRPM8 expression, as well as the full extent of the role of TRPM8 in cold signaling in vivo. These findings will further our understanding of basic thermotransduction and sensory coding, and may have important implications for treatments for acute and chronic pain.


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