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Thursday, 6 February 2020

A specific type of cancer treatment improves night vision, and we finally know why


Following a specific cancer treatment called photodynamic therapy, some patients have reported experiencing differences in their night vision, including the ability to see more clearly or to distinguish objects better in the dark. Photodynamic therapy uses light to destroy cancer cells, and its interaction with certain photosensitive proteins is believed to be the cause of this mysterious side effect.



In a recent study, researchers show their understanding of what would be the cause of this photosensitivity change: rhodopsin, a light-sensitive protein in the retina, interacts with a photosensitive compound called chlorine e6, a crucial component of this type of cancer treatment.

The work is based on what scientists already know about the retinal organic compound, which is located in the eye and is generally not sensitive to infrared light. The results were published in the Journal of Physical Chemistry Letters .


An interaction between rhodopsin and chlorine e6

Visible light causes the rhodopsin to separate from the retina. This is then converted into electrical signals, which our brain interprets to form an image. Although little visible light is available overnight, it turns out that this mechanism can also be triggered with another combination of light and chemical reaction: under infrared light and with an injection of chlorine e6, the retina undergoes the same reactions as under visible light.

"This explains the increase in nighttime visual acuity," said chemist Antonio Monari, from the University of Lorraine in France, to CNRS. “However, we did not know precisely how rhodopsin and its active retinal group interacted with chlorine. It is this mechanism that we have now managed to elucidate via molecular simulation”.

Enhanced color scanning electron micrograph showing rods (in red) and human eye cones (x2500 magnification). Rods are long nerve cells that react to a small amount of light. Cones are shorter cells that detect color. Rods and cones transmit visual signals to the brain through the optic nerve. In theory, rods are not sensitive to infrared radiation, which predominates at night. Credits: Science Source / BSIP


Model the movements of individual atoms to understand the mechanism involved

In addition to certain chemical calculations, the team used molecular simulation to model the movements of individual atoms (in terms of respective attraction and repulsion), as well as the breaking or creation of chemical bonds.

The simulation, which is the subject of millions of calculations, lasted several months before being able to accurately model the chemical reaction caused by infrared radiation. In reality, this reaction would occur in a few nanoseconds.

Screen capture of the digital molecular simulation performed during these experiments. The chemical interaction between the chlorine e6 molecule used for phototherapy and the rhodopsin present in the receptors of the eye is visible. Credits: LPCT / University of Lorraine - CNRS


"For our simulation, we placed a virtual rhodopsin protein inserted into its lipid membrane in contact with several molecules of chlorine e6 and water, involving tens of thousands of atoms," said Monari.

As chlorine e6 absorbs infrared radiation, it interacts with oxygen in the eye tissue, transforming it into singlet oxygen (excited metastable state) very reactive and destroying cancer cells. Molecular simulation shows that singlet oxygen can also react with the retina and temporarily improve night vision.

Treating certain types of blindness or excessive sensitivity to light

Now that researchers are familiar with the chemistry behind this strange side effect, they may be able to limit the risk of this happening in patients undergoing photodynamic therapy, some of whom have reported seeing silhouettes and outlines otherwise. invisible in the dark.

This chemical reaction could also ultimately be used to help & treat certain types of blindness or excessive sensitivity to light. For the moment however, exploiting this still little understood phenomenon to offer a superhuman night vision is more than contraindicated…



"Molecular simulation is already used to shed light on fundamental mechanisms - for example, why certain DNA lesions are better repaired than others?" It also allows the selection of potential therapeutic molecules, by mimicking their interaction with a chosen target, "said Monari.


Bibliography:

Induced Night Vision by Singlet-Oxygen-Mediated Activation of Rhodopsin

Marco Marazzi, Hugo Gattuso, Angelo Giussani, Hong Zhang, Miriam Navarrete-Miguel, Christophe Chipot, Wensheng Cai, Daniel Roca-Sanjuán, François Dehez, Antonio Monari

J. Phys. Chem. Lett. 2019, 10, 22, 7133-7140

Publication Date:October 25, 2019

https://doi.org/10.1021/acs.jpclett.9b02911

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