Cataracts and degenerative diseases of the retina: from science to practice

Paradoxes of vision and salvation in yellow glasses
Marina Muravyeva, STRF.ruNew methods of diagnosis and prevention of common eye diseases – cataracts and degenerative diseases of the retina – are being developed by scientists of the Academic Institute of Biochemical Physics under the leadership of Academician Mikhail Ostrovsky.

The history of the study of the mechanisms of vision is the very history of the development of science, the history of the curiosity of scientists, says Academician Ostrovsky, head of the Laboratory of Physico–chemical bases of reception of the Institute of Biochemical Physics of the Russian Academy of Sciences named after Academician N.M. Emanuel: "Since the time of the ancient Greeks, scientists have been trying to answer a seemingly simple question: how light turns into vision. There is an answer to it, and, strictly speaking, it has always been, but only at the level of knowledge at which science itself was at one time or another."

Physicists have made a huge contribution to the study of the mechanisms of vision. So, back in the XVII century, astronomer and physicist Johannes Kepler described the eye as a "pinhole camera", where the lens is a focusing lens that creates a reduced and inverted image on the retina. "I leave to future natural philosophers the task of understanding how we see the world unturned," Kepler wrote. Other great scientists have also worked on the riddle of vision. It is enough to name Jung, Maxwell, Helmholtz.

In the first half of the twentieth century, it became clear from the works of Russian physicists – Academician Yulia Khariton, and a little later Academician Sergey Vavilov that the visual cell is a kind of living photomultiplier capable of detecting only one quantum of light. Over the past two or three decades, it has been determined exactly how this photomultiplier works, how it amplifies a hundred or even a million times the light signal it receives with a value of only one quantum. In order for a person to see something - even the faintest light flash, it is enough for his retina to absorb only 15-20 quanta.

Russian academician Mikhail Ostrovsky, who took over the baton of research on the mechanisms of vision from his predecessors, is studying a phenomenon that he calls the "photobiological paradox of vision." For many years of fundamental research of vision processes, he was awarded the highest award of physiologists – the I. M. Sechenov Gold Medal of the Russian Academy of Sciences.

The paradox of vision"Light is not only a carrier of visual information, but also a potentially dangerous factor that can damage the structures of the eye," says Academician Ostrovsky.

– Vision, or rather, the ability of the very first primitive organisms to use light as a source of information, arose at the dawn of the evolution of the animal world, that is, about 600 million years ago. And at the same time, mechanisms appeared to prevent the danger of the damaging effect of light. Of course, over the next millions of years of evolution, the visual apparatus improved. And at each subsequent stage of evolution, the photobiological paradox of vision was resolved more and more effectively. Those organisms that failed to adapt died. This is the principle of Darwinian selection. In our case, the sighted one survives."

The components of the molecular "machinery" of vision are extremely vulnerable to the damaging effects of light, if they are not protected, they can burn out from light. Ultraviolet and the violet-blue part of the solar spectrum are especially dangerous for them. The fact is that harmful substances accumulate in the visual cells of the retina and in the cells of the pigment epithelium lying behind it, which effectively absorb blue light. As a result, they are able to form free radicals – active and toxic forms of oxygen, which can lead to devastating consequences. Such harmful substances include the so–called "old age pigment" - lipofuscin, which accumulates with age in the cells of the pigment epithelium. Prior to the research of Academician Ostrovsky and his collaborators (the beginning of the 90s), it was believed that lipofuscin was just inert slags inside the cell. But it turned out that they are far from inert, and under the influence of blue light they become active sources of destructive free radicals. Moreover, the development of severe retinal diseases, leading to partial and sometimes complete loss of vision, is accompanied by a massive accumulation of the "pigment of old age" in these cells. It is more than likely that the aggravating effect of light, well known to ophthalmologists in such diseases of the retina, is precisely due to the accumulation of the "pigment of old age".

How to protect yourself from lightThe photobiological paradox of vision was successfully resolved by nature itself.

Over millions of years of evolution, protection systems have emerged. At least there are three of them. The first and most effective is the photosensitive parts of the visual cell, in which light is converted into a visual signal, are updated approximately every 10-12 days. The second is the so–called antioxidants, which are much more in visual cells than in all other cells of the body, and which protect them from photo-oxidation, from the damaging effects of light and oxygen. These are vitamins E and C, as well as a complex of antioxidant enzymes. And finally, the third is the optical system, in which the lens plays a key role. The lens is not only a focusing lens that provides a clear (and inverted) image at the bottom of the eyeball, but also a very effective light filter that cuts off areas of the optical spectrum.

With age, the lens turns yellow, so the color difference becomes worse in older people, they distinguish blue colors especially poorly – the yellowing lens partially "closes" the blue-sensitive cones (French artist and sculptor Henri Matisse (1869-1954) actively used blue paints in old age). If the lens is transparent and colorless in children, then in the elderly it is transparent (if there are no cataracts) and yellowish, sometimes even with a brown tinge.

Doctors believed that this yellowness accompanies old age, like wrinkles or gray hair, which, in principle, is true. "But at the same time," Mikhail Ostrovsky notes, "it is also an adaptive reaction of the eye, the physiological meaning of which is to cut off from the aging retina a dangerous part of the solar spectrum – not only ultraviolet, but also partially blue."

By the time (early 1980s), when, based on the results of fundamental research, scientists realized that the artificial lens that is inserted into the eye after cataract removal should not be colorless, but yellowish, like a normal lens of a 45-50-year-old person, colorless artificial lenses were implanted in the world. They were made of plastic – polymethylmethacrylate. Simply put, it is plexiglass. Sometimes an ultraviolet ray absorber was added to it, because it was well known that ultraviolet was dangerous for the retina. But usually nothing was added to plexiglass, and it passed all the rays of the solar spectrum to the retina, starting from hard ultraviolet. As a result, a side effect was observed in patients – complications in the form of a "burn" of the retina. Ostrovsky's group suggested that chemists introduce paint into the plex (technically it is not difficult) and make an artificial lens of a yellowish color. Professor Linnik was the first to implant such lenses at the Fedorovsky Ophthalmological Center – MNTC "Eye Microsurgery". Since 1986, more than one million three hundred thousand operations have been successfully performed. As a result, the number of retinal complications decreased, according to the ISTC "Eye Microsurgery", by almost 10 times.

As Academician Ostrovsky notes, the idea of a yellow lens was obvious to his colleagues in physiology, whereas it was a discovery for ophthalmologists. Not so long ago, the famous American company Alcon created soft artificial lenses of the same color. But for the first time, Russian scientists came up with this idea. With 20 years of advance, they have created a new generation of artificial eye lenses that reliably protect the retina from the danger of light damage. In 2005, for the work "Development, scientific justification and introduction into ophthalmological practice of photoprotective artificial lenses with natural spectral characteristics" to Academician Mikhail Ostrovsky (head of the work), Pavel Zak, Professor. Leonid Linnik and the professor. Hristo Takhchidi was awarded the prize of the Government of the Russian Federation in the field of science and technology.

Yellow glasses will helpContinuing the research started in the 80s, Academician Ostrovsky's team planned to create photochromic lenses that would be like a chameleon: colorless in the dark, and yellow on the street.

But it turned out that chemists can't solve the problem yet: photochromic substances that change color work only in glass or a very hard polymer, and you can't make lenses out of glass. Therefore, scientists have begun to create photochromic glasses. The work is carried out jointly with Academician Minkin from the Southern Scientific Center in Rostov and Academician Aldoshin from the Institute of Problems of Chemical Physics of the Russian Academy of Sciences in Chernogolovka. Currently, scientists are selecting spectra, determining which photochromic dyes are needed. These glasses should be colorless at dusk or in dim light, and in bright light they should acquire the color of amber – from light to dark, depending on the intensity of illumination. Such glasses will not only protect the eyes, but also improve the quality of visual perception. However, the fact that yellow light filters, by reducing chromatic aberration, improve image quality is well known to professional photographers: they often use such light filters to make the frame clearer. Such glasses are needed by people who have problems with the retina, and these are usually visually impaired, or those who have colorless artificial lenses implanted after cataract removal. In addition, photochromic glasses are necessary for elderly people who have an increased risk of light damage to the lens and retina. These works are carried out within the framework of a project supported by the Federal Target Program "Research and Development".

In search of the "pigment of old age"Another direction of the project is the development and improvement of new methods for the diagnosis of senile changes and degenerative diseases of the retina.

In particular, there is a very serious and common disease – age-related macular degeneration of the retina, which can lead to complete blindness. Effective ways to treat it have not yet been created. If the lens can be replaced, then the retina cannot. As the Spanish scientist Ramon y Cajal said at the beginning of the last century, "the retina is a part of the brain placed in the eye." And as it is impossible to replace the brain, so it is impossible to replace the retina of the eye, adds Academician Ostrovsky.

The retina, like a Napoleon cake, consists of many layers, the outermost one is a layer of visual cells. Behind them lies the so-called pigment epithelium adjacent to the retina. Since the photosensitive part of the visual cell is constantly being updated, the fragments of this part fall and are digested in the cells of the pigment epithelium. With age, these fragments are digested worse and worse, and therefore accumulate in these cells. Such "undigested" fragments form the "pigment of old age". In diseases of the retina, a huge amount of "old age pigment" accumulates. This pigment has two properties. Firstly, it is phototoxic, and secondly, it strongly fluoresces. Precisely because the "pigment of old age" is phototoxic, it is necessary to cut off ultraviolet and violet-blue light from it, which this pigment effectively absorbs and which is especially dangerous for the senile or diseased retina. The fluorescence of the "pigment of old age" allows us to assess whether a lot of it has accumulated in the pigment epithelium. For this purpose, a very expensive device has been developed relatively recently – a confocal scanning laser ophthalmoscope. It allows noninvasively – and this is fundamentally important - to "catch" this fluorescence. The greater the fluorescence, the greater the "pigment of old age" ("lipofuscin"). According to the degree and localization of fundus fluorescence, it is possible to determine the stages and severity of retinal disease.

"This fluorescent noninvasive diagnosis is extremely effective and completely harmless, and you don't need to inject anything into the blood to then see fluorescence, as they do now," says Mikhail Ostrovsky. – Not all ophthalmological centers in the world have such devices, they are very expensive, and not everyone knows how to work on them competently. We need to understand exactly what this non-invasive fundus fluorescence is talking about. This is what we are doing in order to improve, as they say, "bring to mind" this new diagnostic method. The earlier and more reliably doctors determine the disease, the easier it will be to protect the diseased retina, for example, from the aggravating effect of light, or the more effective the treatment methods that exist and are currently being used."

Academician Ostrovsky emphasizes how important it is that they – physiologists – work closely with physicists and chemists. It was the understanding of the need for such cooperation that led academician, Nobel Prize laureate N.N. Semenov, the founder of the Institute of Chemical Physics, and student – academician N.M. Emanuel, the founder of the Institute of Biochemical Physics, to the fact that they actively gathered scientists of different specialties within the walls of one institute. And it turned out to be extremely fruitful. The success of Academician Ostrovsky's laboratory in the field of fundamental and applied research of primary mechanisms of vision is a clear evidence of this.

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