The lens of the eye is a miracle of nature
Muranov K., Ostrovsky M.*
* NM Emanuel Institute of Biochemical Physics of RAS
First published: In the world of science. 2021. No. 4 (April). P. 52–57.
The lens of the eye is truly a miracle of nature. Not only is it transparent, moreover, for almost all of its life, it is also a living focusing lens that provides a sharp image on the retina. In addition, it is a light filter that cuts off ultraviolet radiation, which is dangerous for it, from the retina.
Quite a long time ago it became clear why the lens is transparent, but it is still unclear how to preserve this transparency, to prevent its clouding, that is the development of cataracts — the most common eye disease in the world. According to the World Health Organization (WHO), cataracts cause blindness in almost 40% of people aged 50 and over.
Of all types of cataracts, "senile" is a constant scourge of aging humanity. Of course, modern high-tech, sophisticated surgery allows you to remove a clouded lens and replace it with a new, artificial one. But the surgery itself can be harmful. Therefore, it is naturally better to prevent cataracts than to operate on them. And for this, you need to understand well why the lens is transparent, by what mechanisms this transparency is maintained, why it begins to grow cloudy. Quite intelligible answers have been received recently to many of these questions.
Why is the lens transparent
The lens of the eye is made of protein. And protein has amazing properties. Its solution at a low concentration, for example, 3 mg per milliliter, is transparent. If you gradually increase the concentration of protein, then the solution will begin to cloud. But if the protein concentration is brought to 300 mg per milliliter, then the solution will become transparent again. And this is a miracle! It turns out that the protein solution is transparent both at a low concentration of 3 mg per milliliter and at a concentration 100 times higher. Colloidal chemistry (and a protein solution is a colloidal solution) provides a fairly simple explanation. Due to Brownian motion, protein molecules move, forming zones with increased and decreased concentration. Light scatters, passing through such zones, here it is — a colloidal solution! As the concentration of the protein increases, the distance between its molecules will decrease and ultimately will be reduced so much that the protein solution acquires a crystal-like structure. And the crystal, as you know, is transparent. That is why, according to the laws of colloidal chemistry, the lens is transparent, because the concentration of protein in it is incredibly high — 450 mg per milliliter in humans and 900 mg per milliliter in mice!
It should be noted that it is transparent not for ultraviolet radiation, but in old age — even not for the violet-blue rays of the visible spectrum. True, in infancy and childhood, the lens is partially transparent to ultraviolet radiation and violet-blue rays. In the physiology of vision, this transparency is called the "ultraviolet window". And ultraviolet light is destructive for the retina. This danger for children has become especially acute in connection with the widespread use of LED lighting and liking for it. The light of "cold" violet-blue LEDs, penetrating through the "ultraviolet window" of a child's lens, can cause unpredictable and most adverse effects on vision.
A middle-aged adult has no "ultraviolet window" anymore, and his lens, holding back ultraviolet light, freely passes all the rays of the visible spectrum to the retina. However, closer to old age, a normal healthy lens, while continuing to remain transparent, begins to turn yellow. And this is the greatest blessing for the retina because by old age, in the retina and the so-called pigment epithelium lying behind it, accumulate substances that absorb light in the violet-blue region of the spectrum. After absorbing light, these substances form active toxic forms of oxygen. In other words, they are phototoxic. The lens, which turns yellow with age, more and more traps the violet-blue rays, protecting the retina from the danger of photodamage.
How is the transparency of the lens maintained and why it becomes cloudy
One of the proteins of the lens itself plays a key role in the transparency protection system. The fact is that there are several types of crystalline proteins in the lens. The main ones are alpha-, beta-, and gamma-crystallins. Moreover, beta and gamma-crystallins stick together and aggregate very easily. If this happens, the transparency will disappear, the lens will become cloudy. Alpha-crystallin maintains transparency, prevents beta- and gamma-crystallins from sticking together, forming aggregates — lumps. But as soon as the alpha-crystallin deteriorates a little, it loses the ability to keep the beta- and gamma-crystallins from aggregating. As a result, the lens begins to grow cloudy. This is the mechanism of cataract formation.
Alpha-crystallin belongs to the class of so-called chaperone proteins. Chaperones can restore the normal (native) structure of a damaged protein, in other words, “repair” damaged proteins. To understand exactly how this happens, first of all, you need to know how they are arranged, that is, their three-dimensional structure.
The alpha-crystallin molecule has something like a cavity inside it. This cavity includes damage (in our case — by ultraviolet) these molecules of beta- and gamma-crystallins. Inside the cavity, the lesions are "treated", the original, native structure of the protein is restored. As a result of the "treatment", the molecules of beta- and gamma-crystallins do not stick together — the solution remains transparent, and even if it becomes cloudy, it is much slower.
Scattering of blue light by solutions of alpha-crystallin of different concentrations: A — 3 mg per 1 ml; B — 54 mg per 1 ml; C — 300 mg per 1 ml
However, with age, both the protective activity of alpha-crystallin and its amount in the lens decrease. Therefore, it is no longer able to effectively keep beta- and gamma-crystallins from aggregation. This is the reason for the onset and development of senile cataracts.
Apart from alpha-crystallin, natural antioxidants and antioxidant enzymes are included in the lens transparency protection system. The fact is that reactive oxygen forms, attacking a protein molecule, damage it. Fortunately, there is practically no oxygen in the lens. But when exposed to various cataractogenic factors, including ultraviolet radiation, oxygen reaches the proteins of the lens and its active forms spoil the proteins — they oxidize. As a result of such damage, the lens becomes cloudy. Therefore, antioxidants and antioxidant enzymes of the lens itself are the most important line of defense against cloudiness.
Cataracts are not only caused by old age. Quite a lot of its causes are known: this is diabetes and various types of radiation — from ultraviolet radiation and X-rays to heavy charged particles of galactic radiation and some other factors. It would seem that the mechanism of cataract occurrence should depend on the nature of the damaging factor. However, it is not. Various cataractogenic factors (radiation, ultraviolet light, high blood sugar, etc.) damage the cells of the outer epithelial layer of the lens. As a result, gaps are formed in this layer, through which oxygen begins to penetrate the lens. As we stated, normally, there is practically no oxygen in the lens. In the presence of oxygen, mitochondria, still preserved in the cells of the cortical part of the lens, begin to produce reactive oxygen forms, which cause oxidative damage to proteins. Oxidized proteins tend to aggregate. At some point, when the compensatory defense system fails, proteins begin to denature and aggregate. The formed aggregates, like all the growing lumps, turn into the so-called multilamellar bodies. These bodies scatter light themselves and disrupt the crystal-like packaging of lens proteins. The lens ceases to be transparent — a cataract occurs.
How to prevent cataracts
Despite the existence of many types of anti-cataract drops, they cannot prevent cataracts. And now it becomes clear why. The thing is that drops begin to drip into the eye, as a rule, when the lens has already become unclear. This means that oxygen has already done its dirty work, and alpha-crystallin is no longer able to prevent the aggregation of beta and gamma crystallins. And if these crystalline proteins collapsed, stuck together, formed aggregates, multilamellar bodies, then it is impossible to reverse the situation.
What can be done to delay, prevent lens clouding?
First, you need to catch the moment when the lens proteins are just starting to aggregate. Secondly, it is necessary to create an anti-cataract drug that would simultaneously prevent proteins from oxidizing, and, like natural alpha-crystallin, would prevent the aggregation of beta and gamma-crystallins.
To catch the moment when the proteins of the lens are just beginning to aggregate, you need to "look into the eye." This can be done using a modern optical device, which we tentatively called "Cataractomer". The essence of his work is that by analyzing some characteristics of light scattered by the lens, one can "see" both a decrease in the number of alpha-crystallin molecules and the appearance of protein aggregates in the lens.
The main principle of operation of such a device is the registration of light scattered inside the lens. Several designs of such tools have been created. One of these designs, developed by Professor Rifat Anzari of NASA, is already undergoing clinical trials.
Let's hope that shortly, during a routine preventive check-up, the doctor, after a ten-minute examination, will be able to tell the patient that he is at risk and that it would be quite nice to immediately start dripping anti-cataract drugs into the eye.
What to drip
We focused our efforts on creating a drug that would help alpha-crystallin to prevent the aggregation of beta and gamma-crystallins. We have recently developed such a combined medicine. It is based on two substances — N-acetyl carnosine and pantethine.
Why N-acetyl carnosine? It is a carnosine derivative. Carnosine and, to a greater extent, N-acetyl carnosine do not so much prevent the oxidation of proteins as effectively inhibit their aggregation, and at very low concentrations.
In other words, N-acetyl carnosine exhibited chaperone-like properties similar to those of alpha-crystallin.
Why pantethine? It turned out that it significantly increases the ability of alpha-crystallin to protect damaged proteins from aggregation. In collaboration with the staff of the Research Institute of Eye Diseases, we studied in detail the anti-cataract effect of our complex drug in vivo. In a rat model of ultraviolet cataract, it has been shown that a mixture of N-acetyl carnosine and pantethine is indeed effective in preventing the development of cataracts.
A combination of antioxidant and chaperone-like drugs can be effective in preventing cataracts. It is quite obvious that impressive advances in understanding the nature of lens transparency and its maintenance, knowledge of the mechanisms of violation of this transparency will soon lead to the development of effective drugs for the prevention of cataract. And then its surgical treatment — replacing the clouded lens with an artificial one — will cease to be the only and inevitable way to restore vision to sick people.
The lens is truly a miracle of nature, and it must be protected as it should be.
Anti-cataract effect of a mixture of N-acetyl carnosine and pantethine: A — ultraviolet cataract in a rat, green arrow marks lens opacities, blue arrow — a light reflection of the illuminator;
B — transparent lens after treatment