Cell XIX. Returning vision to a person

Just yesterday, things that seemed fantastic are becoming reality today. Biotechnology continues to amaze the world with its achievements. Here we will talk about the return of lost vision. The reasons for such a loss can be very diverse: injuries, accidents, illnesses, etc. The path to recovery can also vary.

According to the International Agency for the Prevention of Blindness, today approximately 284 million people on Earth have some form of visual impairment, about 39 million of them are completely blind. Blind people learn to interact with the world and live actively, regardless of their vision impairment. It is estimated that only 2% to 8% of blind people use a cane to navigate. Others rely on a guide dog, partial vision, or a sighted assistant. Besides navigation, blind people can do almost everything that sighted people can do: prepare food, apply makeup, use a computer. With the help of accessible technology and gadgets and their own willpower, blind people can be independent.

More than a quarter of all blind people suffer from neurodegenerative diseases of the retina, when visual cells die. In Russia, the number of blind and visually impaired people exceeds 210 thousand. According to forecasts, these numbers in the world will grow significantly in the coming decades. Already, every year approximately 45 thousand people become disabled due to vision problems. More than half of them are children and adolescents under the age of 18.

Scientists all over the world are racking their brains to solve the problem of blindness – how to stop the loss of vision and how to return it to people who are already blind. People with severe vision loss access the computer (Internet) using assistive technology in two different ways. The first method is to use a Braille display, which connects to a computer and converts text to Braille line by line. The second method is a screen reader that reads the information out loud. This is also implemented on smartphones that have technologies such as TalkBack or VoiceOver.
There are other approaches to solving the problem.

Introduction

There is another approach – optogenetics. Optogenetics – a technique for studying the work of nerve cells, based on the introduction of special channels into their membrane – opsins that respond to excitation. Optogenetics – a fantastic way to control certain cells of a living organism (most often nerve and muscle) using light. The first anion channel rhodopsins have now been discovered. These proteins, under the influence of light, allow chlorine ions to pass into the cell, which leads to hyperpolarization of the membrane and, consequently, suppression of the electrical activity of excitable cells. Thus, it became possible with light not only to excite cells, but also to inhibit excitation in them.

Previously, channel rhodopsins were known to selectively allow entry into cells. cations (positively charged ions), which leads to excitement neuron (you can read more about this in the article “Bright head» [1]). Only very recently, scientists managed to find channel rhodopsins, through which only anions (negatively charged ions). Thus, it has now become possible not only to effectively stimulate, but also suppress activity nerve cells using light.

Optogenetics allows, through the use of promoters specific to a given type of neurons, to excite only them – regardless of how many other neurons are nearby, and without introducing any disturbances into the structure of the cell. In addition, the stimulating light beam can be focused down to the size of a single cell, allowing it to selectively and non-invasively stimulate or inhibit specific neurons.

The company’s specialists approach the problem differently Neuralink. The Neuralink project was launched in 2016. Neuralink is about to release a chip that will allow people to restore their vision. Elon Musk's company Neuralink, which develops neurochips for controlling devices with thoughts, plans to release a similar device for people with visual impairments. reports The Independent.

Neuralink's main goal is to empower people, especially those who suffer from neurological diseases. According to Musk, the device will help control hormones, cope with anxiety, and can even make the brain work more efficiently. The company's main merit is that the team managed to make the chip minimally invasive and create a completely wireless interface. Neuralink plans to develop a similar product for blind people to help them see. According to Musk, this project will be called Blindsight.

In July 2019, the company first demonstrated a device capable of transmitting brain signals via Bluetooth. In 2021, the company published footage of a monkey named Pager playing video games using a chip embedded in its brain.
In January 2024, Musk announced that the neurochip had been implanted into a human for the first time; he was 29-year-old Nolan Arbaugh, paralyzed from the shoulders down due to an accident. In February, it became known that the patient had fully recovered and was able to control a computer mouse with the power of thought. March 21 Arbo showedhow he plays computer chess with the power of his thoughts.

Neuroimplant company ELVIS. – This is a large, knowledge-intensive and breakthrough project for Russia – a neuroimplant that allows partially restoring vision to blind people. Fundamentally, this works according to a fairly simple principle, which has long been tested in medicine: if you stimulate the visual cortex with weak currents, a blind person will see flashes of light in their consciousness. This is how the human brain works: it responds to the stimulation of neurons in the brain by interpreting these electrical impulses in the format of light flashes.

The main goal of the ELVIS project is to make a convenient medical product that is safe and that the patient can use all the time. The system consists of three components: the patient puts on a headband with cameras that capture the surrounding image; a microcomputer is placed on the belt, which processes data from cameras in real time and converts them for transmission to the brain; Electronics are implanted into the brain and under the skin, which receives information from external parts of the system and stimulates the brain with electrical impulses. Patients will see a black and white image where the entire world is in the form of lines and contours. It’s as if all objects, objects, people, etc. were outlined along the contour.

The work of the eye and brain

How do the eyes and brain work? How do we see the world around us? The retina is essentially a part of the brain located outside the skull and into the eye. The retina of the human eye has approximately 7-8 million cones, responsible for color vision, and about 120 million rods (black and white vision). This corresponds to approximately 250 megapixels for a visual panorama.

The optic nerve (1,200,000 nerve fibers) of the eye is occupied by the transmission of excitation impulses by the flow of light from these layers to the brain. With a frequency of 100-150 Hz, the image is transmitted frame by frame to the visual cortex of the brain. Assuming that the nerve fiber transmits 1 bit/cycle, the total bandwidth of the optic nerve will be 1.2 * 10⁶ *150 = 180 megabits/s. And the brain already receives 360 megabits/s from the two eyes, and also has its own streams from other systems. All this load fits into just 25 watts. At the same time, it is not entirely clear how ≈125*10⁶ receptor cells can transmit information in ≈1.2*10⁶ conducting neurons.

That is, even before transmission to the brain, some filtering and preprocessing of visual information occurs. The delay in the conduction of the nerve impulse to the processing centers is, according to various estimates, approximately 150-180 ms, i.e. we always see past. The retina is made up of many layers, each layer performing a specific function. The structure of the eye itself is second in complexity only to the brain itself. The first layer is photosensitive, the next two are nerve cells, bipolar and ganglion.

rice. 1. Conducting pathways. Retinal neural network and electrical responses of cell types

Bipolar cells connect receptor and ganglion cells. The function of bipolar cells is to conduct excitation from photoreceptors to ganglion cells. The function of ganglion cells is to conduct excitation from the retina to the central nervous system. Two branched processes extend from the bipolar cell body: one process forms synaptic contacts with several photoreceptor cells, the other with several ganglion cells.

The main layer for vision is the first. These are the visual cells known to us from school: rods and cones. They contain a photosensitive substance – the protein rhodopsin.
This protein reacts when a quantum of light enters the eye and absorbs it. Then amazing things happen; a complex biochemical reaction system is activated, which produces a response (Fig. 1, part B) in the form of an electrical impulse even to a single quantum of light. The signal in the photosensitive layer is amplified 100 thousand times. It goes for primary processing to the nerve cells of the eye, and then to the brain, where the visual image is formed.

The brain is economical; it forms an image “pixel by pixel” in the most difficult situations (the most expensive mode). Usually the brain tries to pick up a similar picture from memory, i.e. from what was previously seen. And only when the understanding comes that the discrepancy is very large, the corresponding construction begins.

“The fact is that the main task of the brain is not development, not the search for optimal solutions, not thinking about situations. Everything is much simpler and more prosaic. The brain is interested in maintaining the vitality of the body, achieving this in the simplest way and spending a minimum of energy. Therefore, it often the beginning of any new business is accompanied by a state of anxiety, the emergence of fears and doubts. This is the brain sabotaging the task, which forces it to leave the comfort zone.”

In the retina (in its nerve cells), the most complex processing of primary visual information and its encoding occurs. Information presented in this form (impulses) is transmitted to the brain. When the retina is in normal condition, this is how the eye works. When the condition of the retina changes (during disease) due to the destruction and death of cells in the light-sensitive layer, blindness occurs.

What and how to do for those who have lost their sight

A hereditary disease is known – retinitis pigmentosa, associated with degeneration of retinal cells. It causes progressive vision loss. There is no effective treatment for retinitis pigmentosa today. A significant proportion of cases of this disease are associated with disorders in the gene encoding rhodopsin. This gene is important for the functioning of two types of receptor cells in the retina. These are rods, which have good light sensitivity, but are not capable of providing color vision, and cones, which allow one to distinguish color, but are less sensitive to light intensity. In patients with retinitis pigmentosa, rod cells die rather quickly, but cones, having lost the ability to perceive light, live for a long time.

Now science is giving a chance to restore vision to those whose retina, its first layer, has been lost or destroyed. This chance is provided by optogenetics – a technique for studying the work of nerve cells, based on the introduction of special channels into their membrane – opsins that respond to excitation by light. The idea of controlling neurons “pointwise” was first clearly expressed in 1979 by Francis Crick (who received the Nobel Prize for the discovery of the structure of DNA). Twenty years later, in 1999, he proposed using light to excite neurons.

A problem arose – how to deliver light exposure (impulses) to the brain to the nerve cells. A very simple and obvious way is to drill into the skull and insert a light guide fiber.
In addition, there is a problem in supplying brain cells with rhodopsin.
There are two ways to deliver the rhodopsin gene into brain cells. The first involves obtaining a transgenic organism. For example, the rhodopsin gene can be inserted into the mouse genome at the embryonic stage, and then all cells of the body will contain it. But this gene will not work in all cells, but only where it is activated. Gene activity can be controlled.
A transgene is a DNA fragment transferred using genetic engineering manipulations or nature into the genome of a certain organism in order to modify its properties. The transgene can be isolated from a biological object or synthesized artificially.

The second method of delivering the gene into cells works much faster. It uses viruses that carry the rhodopsin gene. If a safe, sufficiently large amount of the virus is introduced into the brain and penetrates the neurons, the production of light-sensitive proteins occurs very efficiently. A separate task is the delivery of light to neurons located deep in the brain. In most cases, fiber optic light guides are used for this.

The only area of medicine where optogenetics methods can reach the clinic is ophthalmology. After all, light enters the cells of the retina naturally. The skull does not need to be drilled.

How it is proposed to restore vision. Previously, they even thought about an eye transplant, like a kidney transplant, heart transplant, etc. But in practice this is not realistic. The eye is a very complex organ. The new idea is as follows. Behind the dead photosensitive first layer of retinal cells, there is a layer with healthy cells. Is it possible to make these cells photosensitive? To do this, the protein rhodopsin must be “inserted” into them. Today this is no longer fiction, in genetics it is reality.

Used a virus harmless to the body, which plays the role of transport. on him hung the rhodopsin gene and another element that causes this gene to come to a specific address – to nerve cells. And when light hits them, they give off impulses that go to the brain. At the same time, the eye senses the light entering it and reacts with impulses.
But the eye does not see clearly. It's not that simple.

Processing of primary information occurs in the nerve cells of the retina. So, when cells, having received rhodopsin, become photosensitive, they directly send impulses to the brain, and there is no longer any information processing. The brain reacts to this “noise”, but the visual image does not arise. However, the brain itself gives a chance for insight. This amazing organ has amazing plasticity, which allows it to find a way out in the most difficult situations.

There are numerous amazing cases where, when some areas or even an entire hemisphere of the brain were damaged, the brain was able to restructure itself: its healthy areas took on the lost functions. If vision is restored, thanks to the plasticity of the brain, it can use primary information unprocessed in the nerve cells of the eye. In experiments, this was shown on blind mice: they were injected with the rhodopsin gene, and they regained their sight and were able to get out of a complex maze. Electrical activity appeared in the areas of their brains responsible for vision.

It is clear that you cannot ask the mouse what it began to see. An experiment conducted by Swiss and French scientists in 2021 became a global sensation. They inserted the rhodopsin gene into a blind man and he began to see: he was able to see a pedestrian crossing and count the number of white stripes, saw plates, mugs, a telephone, pieces of furniture in the room, doors in the corridor.

The gene for rhodopsin, not from a human, but from a single-celled algae, was introduced into the eye. In the mouse, this rhodopsin gene from algae, although it had light sensitivity, was very low. In order for a person to see, scientists had to make a complex and massive system in the form of glasses that amplified this signal. This is not suitable for mass use.

The fact is that all optogenetics began with the algal rhodopsin gene. Most neurobiological research, including in ophthalmology, continues with it. Currently, there has been a transition to rhodopsin in the rods and cones of the retina. It is fundamentally important that it has a thousand times higher sensitivity to light than algae rhodopsin. This use will not require such a complex amplifier.

The main thing that turned out to be both in experimental animals and now in humans is that this technology works in principle. Of course, this technology will not come to clinics tomorrow, but in five years it is quite possible. Most likely, the person will not be able to read or work on a computer. But he will distinguish the situation in the apartment, and most importantly, he will see other people.

Previously, light-controlled devices were used for optogenetic manipulations. sodium
channels through which nerve cells could be activated. And now bioengineers have created a light-controlled potassium a channel with which you can, on the contrary, reset the potential on the membranes of neurons and other cells.

Scientists plan that future generations of retinal prostheses should include not only higher resolution, but also a digital visual impulse encoding unit that translates the usual image into the language of impulse sequences perceived by ganglion cells. You can even fantasize and imagine various “firmware” of such a block, providing better visual acuity or some special visual effects that are inaccessible to truly sighted people

At the same time, it is proposed to improve not only the system of genetic transformation of ganglion cells with photosensitive proteins or the method of encoding signals for them. Researchers from the Israel Institute of Technology (Technion) develop a system holographic stimulation of ganglion cells, which has a number of advantages over the already mentioned “mini-projectors”. These are high intensity, uniform illumination (no need for scanning systems), low power consumption, high resolution and the ability to create a three-dimensional picture of the excitation.

Indeed, to transmit the “retinal code” to ganglion cells, it is necessary to pulse illuminate very small areas of space (a few micrometers in size) with the ability to quickly switch and focus on different layers of cells – unlike rodents, in humans the ganglion layer is not flat, but three-dimensional. In addition, ganglion cells with channelrhodopsin are still not natural photoreceptors, and their sensitivity is much worse than that of our rods and cones. Therefore, the high brightness and control accuracy of a holographic system is an extremely important advantage over a mini-projector or simply an electronic display built into glasses.

Scientists have created an experimental setup for holographic stimulation of retinal ganglion cells, based on a laser whose beam is modulated by a computer-controlled liquid crystal ferroelectric chip. This device makes it possible to control diffraction and simultaneously “address” hundreds to several thousand “pixels” in the ganglion layer to stimulate visual impulses. (Of course, in this case we are also talking about ganglion cells expressing channelrhodopsin and excited by light.)

Conclusion

Today we can be inspired by scientific progress that can reverse the loss of one of our most important senses. Based on this inspiration, you can gain an understanding of futuristic ideas transhumanismpromising a person in the future a complete upgrade of his mortal body using more modern components.