Thermal imager in the retina
GM mice with thermoreceptors in their eyes acquired infrared vision
Daria Spasskaya, N+1
Swiss scientists have proposed to treat visual impairment by expanding its capabilities to the infrared range. To test the concept, genetically modified thermoreceptors were expressed in the retina of blind mice, which were activated with a laser. According to the authors of the article in Science (Nelidova et al., Restoring light sensitivity using tunable near-infrared sensors), immediately after the laser flash, the mice were able to distinguish an object in front of them.
The cause of vision loss in old age is often the degeneration of photoreceptors in the retina of the eye. Photosensitive mammalian cells perceive visible light with wavelengths in the range of 390-700 nanometers.
Researchers from the Institute of Molecular and Clinical Ophthalmology in Basel, led by Daniel Hillier and Boton Roska, have proposed an unusual solution to restore the ability to navigate in space – to supplement the photosensitive proteins of retinal cells with thermosensitive channels that would allow them to perceive infrared radiation with a wavelength of about 900 nanometers.
In nature, some snakes have this ability, although they perceive infrared radiation with a wavelength of 1 microns not with their eyes, but with the help of a special organ. Visual and thermal information are combined in the snake's brain and allow it to perceive the environment with greater resolution than just with the help of vision. At the same time, ion channels from the TRP (transient receptor potential) family are responsible for their temperature perception, which begin to conduct current when heated. Theoretically, these proteins can be expressed in retinal cells, but their activation requires too powerful radiation, which can damage tissues.
To increase the sensitivity of TRP channels, bioengineers sewed an amino acid sequence to them, recognized by a specific antibody. In turn, gold nanoparticles were attached to the antibody, which would enhance radiation due to surface plasmon resonance. The resulting system would enable the channels to be activated by radiation with less energy and protect the retina from damage.
The scheme of retinal activation using a thermoreceptor embedded in the membrane and nanoparticles conjugated with antibodies against it. Drawings from an article in Science.
In the "field" experiment, the researchers used a rat TRPV1 protein or a Texas poloz protein in combination with nanoparticles absorbing wavelengths of 915 nm or 980 nm in the near infrared region. After testing on cells, the genes of the modified ion channel as part of the viral vector were injected into the retina of model mice. The experimental animals carried a mutation in the genome that led to almost complete degeneration of photoreceptors in adulthood. As a result of the introduction of the virus, about half of the cones in the retina received a modified TRPV1. Antibodies with nanoparticles were injected into the eye separately.
The researchers successfully detected the calcium current in the cones in the presence of nanoparticles under the influence of radiation, and also observed the activation of neurons of the ganglion layer of the retina. However, the successful operation of the system would indicate only the restoration of the ability to distinguish objects in experimental animals, and the researchers confirmed it as follows. Control mice and mice with thermoreceptors in the retina had their heads fixed and were not allowed to drink for a while, and then they shone a laser into the eye and offered a drinker.
It was believed that an animal can actively use a drinking bowl only if it sees it. Indeed, in the experiment, only mice expressing thermoreceptors started drinking, from which the researchers concluded that the method works. However, the authors of the article did not mention anything about the ability to navigate in space in such mice, so we can assume that the possibilities of such "infrared vision" still leave much to be desired.
The scheme of a behavioral experiment to test the activation of thermoreceptors. The graph on the right reflects the frequency of lapping from the drinker after the pulse (NIR) by GM mice (orange and black dots) compared to the control ones (gray dots).
In addition, the researchers tested modified thermoreceptors on the blind human retina ex vivo (that is, outside the body). Retinal samples taken posthumously were cultured in the laboratory, and after a while they lost their ability to respond to light. After that, modified TRPV1S were expressed in photoreceptors using viral delivery and the ability to respond to irradiation at 915 nm in the presence of nanoparticles was tested. Scientists were able to detect calcium currents both in photoreceptors and in the underlying layers of neurons, which meant successful signal transmission.
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