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<h1>The transparency of life: Cataracts as a model of age-related disease</h1>
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<hr>
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<p class="nav"><span class="nav-left">Listed under <a href="/ray-peat.html">Ray Peat</a>.</span><span class="nav-right"><a href="/theme.html">Theme</a></span></p>
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<p>From the <a href="https://raypeat.com/articles/aging/transparency-cataracts.shtml" target="_blank">original article</a> in 2006. Author: <a href="https://raypeat.com/" target="_blank">Ray Peat</a>.</p>
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<em><p>Cataracts
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can disappear when the eye's metabolic condition is corrected.
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A supply of energy is essential to maintain the transparent structure.</p>
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<p>Lactic acid
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increases as carbon dioxide decreases, during a typical energy deficiency.
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Deficient thyroid, and the resulting excess of cortisol relative
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to pregnenolone and progesterone, define the energy deficiency.</p>
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<p>Increased
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lactate relative to CO2 in the cell alters cell pH and electrical charge,
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causing swelling. Swelling and increased water content characterize
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the cataract.</p>
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<p>High altitude
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is inversely related to cataracts, despite the known role of sunlight
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in causing cataracts; this is a strong confirmation of the protective
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role of carbon dioxide.</p></em>
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<p>In
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the markets around Lake Patzcuaro, they sell green transparent fish,
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about 6 inches long. When cooked, the meat is white, like ordinary
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fish. Most fish filets are a little translucent, but are at least
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cloudy, and usually pink by transmitted light. I don’t know
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how the transparent fish work, because it seems that the blood and the
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network of blood vessels needed to sustain muscle activity would diffuse
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the light. Anyway, cooking disrupts the mysteriously ordered state
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of water and proteins that makes them transparent, roughly the way egg-white
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loses its transparency when it is cooked. I have never heard a
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convincing explanation for the opacity of cooked egg-white, either,
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but anything that disrupts the original structuring of the protein-water
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interaction will destroy the transparency.</p>
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<p>Around
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1970, I used a technique called nuclear magnetic resonance (NMR), which
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is the basis for the procedure known as MRI (magnetic resonance imaging),
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to compare the state of water in old (uterine) tissue and young tissue.
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Old tissue predictably contains less water than young tissue, but I
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found that the water in the old tissue was in a relatively free and
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uncontrolled state. When tissue swells and takes up water, more
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of the water is likely to be in this uncontrolled state, and this is
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one of the things that makes MRI so useful, because tumors, for example,
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show up vividly because of their large amount of uncontrolled (“unbound”)
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water. I suspect that the measurements I made on uterine tissue
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showed a localized effect, that opposed the general trend toward increased
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dryness with aging. In the case of cataracts, this is clearly
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the case<strong>: </strong> Most of the lens becomes drier with age, but at a
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certain point there is a reversal, and some of the tissue takes up too
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much water. That’s why I refer to cataracts as a model of age-related
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disease, rather than as a model of aging. In this sense, I am
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including them among the inflammatory diseases of aging--colitis, arthritis,
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and cancer, for example. MRI now can show developing cataracts
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before they are visible, because of increased water content in the area.</p>
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<p>The
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lens of the eye is a fairly dense, tough, transparent living structure,
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which can develop opaque areas, cataracts, as a result of old age, poisoning,
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radiation, disease, or trauma. The varieties of cataract relate
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to the causes. Most of the oxidative metabolism of the lens is
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in or near the epithelial layer that surrounds it. Old-age cataracts
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most often begin in this region.</p>
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<p>Although
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the efficient oxidative energy metabolism occurs near the surface of
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the lens, <strong>there is a constant flow of fluid through the lens,</strong>
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entering it mainly in the front and back, and leaving on its “sides”
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or equator (considering the front and back as the poles, the direction
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light passes through). Oxygen and nutrients are supplied to the
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lens by way of this circulation of fluid, entering mostly from the aqueous
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humor in front (which also supplies the cornea), but also from the vitreous
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humor behind the lens.</p>
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<p>When
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the flow of nutrients and energy is impaired, the organized state of
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the protein and water system in the cell is damaged, and an excess of
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water is taken up by the cells, as the protein content decreases.
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The loss of organization causes light to be dispersed, with a loss of
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transparency.</p>
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<p>The
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lens of the eye is usually treated as something so specialized that
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it is hardly considered to be part of our living substance, just as
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dentistry has tended to treat teeth as inert things to be approached
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mechanically, rather than physiologically. <strong>The lens’s circulatory
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system is very interesting, because of what it says about the nature
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of living substance. In the absence of blood vessels, it provides
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its own flow of nutrients.</strong> This flow is reminiscent of the
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flow of substances through the dentine channels of the teeth, through
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the axons of nerves (two-way transport in a very narrow channel), and,
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in some ways recalls the flow of fluids in plants, called “guttation”
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(drop formation), which is disturbing to botanists,
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because it is contrary to the textbook descriptions of proper physiology.</p>
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<p><strong>The
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flow of material through lens cells, dentine canals, and nerve axons
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should allow us to gain a perspective in which these observable processes
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become a model for other biological situations</strong> in which “transport”
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occurs<strong>:</strong> Kidney, intestine, or the skin of frogs, for example,
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in which water, ions, and other solutes are moved in considerable quantities.</p>
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<p>
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When cells metabolize, they create gradients. In the cell, electrical,
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chemical, osmotic, and thermal gradients, for example, are constantly
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being produced or maintained. The whole substance of the cell
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is involved in its life processes. Because of prejudices introduced
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200 years ago, the life of the cell has been relegated to its “membrane”
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(where hypothetical “membrane pumps” reside) and its nucleus. <strong>
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When the term “cell” (hollow space) came into use instead of “corpuscle’
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(little body), a mind-set came into existence that discounted the importance
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of most of the living material,</strong> and claimed that it was a mere “random
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solution.” Random solutions don’t do much. The wonderful
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“membrane,” under the direction of the nucleus (and its set of instructions),
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took care of everything. </p>
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<p>Whenever
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assimilation or excretion took place, it was explained by inventing
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a property possessed by the cell “membranes.” Therefore, we
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have physiology textbooks that have an unfounded explanation for everything.
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Before Copernicus, planetary movements were described as arbitrary "epicycles."
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They didn't make sense, but people studied them and felt that they were
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important. "Membrane physiology" is the modern equivalent
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of the Ptolemaic epicycles. </p>
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<p>We
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know that glucose can be metabolized into pyruvic acid, which, in the
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presence of oxygen, can be metabolized into carbon dioxide. Without
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oxygen, pyruvic acid can be converted into lactic acid. The production
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of lactic acid tends to increase the pH inside the cell, and its excretion
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can lower the pH outside the cell.</p>
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<p>The
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decrease of carbon dioxide that generally accompanies increased lactic
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acid, corresponds to increased intracellular pH. Carbon dioxide
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binds to many types of protein, for example by forming carbamino groups,
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changing the protein conformation, as well as its electrical properties,
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such as its isoelectric point. With increased pH, cell proteins
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become more strongly ionized, tending to separate, allowing water to
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enter the spaces, in the same way a gel swells in an alkaline solution.</p>
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<p>The
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Bohr-Haldane effect describes the fact that hemoglobin releases oxygen
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in the presence of carbon dioxide, and releases carbon dioxide in the
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presence of oxygen. When oxygen is too abundant, it makes breathing
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more difficult, and one of its effects is to cause carbon dioxide to
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be lost rapidly. At high altitude, more carbon dioxide is retained,
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and this makes cellular respiration more efficient.</p>
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<p>The
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importance of carbon dioxide to cell control process, and to the structure
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of the cell and the structure of proteins in general suggested that
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degenerative diseases would be less common at high altitude. Wounds
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and broken bones heal faster at high altitude, but the available statistics
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are especially impressive in two of the major degenerative conditions,
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cancer and cataracts.</p>
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<p>
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The two biggest studies of altitude and cataracts (involving 12,217
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patients in one study, and 30,565 lifelong residents in a national
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survey in Nepal) showed a negative correlation between altitude and
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the incidence of cataract. At high altitude, cataracts appeared
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at a later age. <strong>In Nepal, an increase of a few thousand feet
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in elevation decreased the incidence of cataracts by 2.7 times.
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At the same time, it was found that exposure to sunlight increased the
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incidence of cataracts, and since the intensity of ultraviolet radiation
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is increased with altitude, this makes the decreased incidence of cataracts
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even more important.</strong></p>
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<p>All
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of the typical causes of cataracts, aging, poisons, and radiation,
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decrease the formation of carbon dioxide, and tend to increase the formation
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of lactic acid.<strong> Lactic acid excess is typically found in eyes
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with cataracts.</strong></p>
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<p>The
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electrical charge on the structural proteins will tend to increase in
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the presence of lactic acid or the deficiency of carbon dioxide, and
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the increase of charge will tend to increase the absorption of water.
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</p>
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<p>The
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lens can survive for a considerable length of time <em>in vitro </em>
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(since it has its own circulatory system),<em> </em>
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so it has been possible to demonstrate that changes in the composition
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of the fluid can cause opacities to form, or to disappear.</p>
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<p>Oxidants,
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including hydrogen peroxide which occurs naturally in the aqueous humor,
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can cause opacities to form quickly, but they will also disappear quickly
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in a solution that restores metabolic energy. The lens regulates
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itself powerfully<strong>;</strong> for example, it will swell when put into a
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hypotonic solution, but will quickly adapt, returning to approximately
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its normal size.</p>
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<p>Several
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years ago, I saw what appeared to be oxidant-induced cataracts.
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Two women had a very sudden onset of cataracts, and I asked about their
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diet and supplements<strong>;</strong> it turned out that one of them had begun
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taking 500 mg of zinc daily a few months earlier, and the other had
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begun taking 600 mg of zinc and 250 mg of iron, on her doctor’s recommendation,
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just a couple of months before the cataracts appeared.</p>
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<p>For
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some reason, there have been many nutritional supplements sold as cataract
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remedies in the form of eye drops. I suppose a trace of the material
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could diffuse through the cornea into the aqueous humor, where it might
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make a difference in the lens’s nutrient supply, but it seems more
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reasonable to treat the body as a whole, nourishing every part in a
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balanced way.</p>
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<p>Besides
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living at a high elevation or breathing extra carbon dioxide, the most
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certain way to increase the amount of carbon dioxide in the eye, and
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to prevent an excess of lactic acid, is to make sure that your thyroid
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function is adequate.</p>
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<p>One
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man who took thyroid, USP, and vitamin E told me that his cataracts
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had regressed, but I haven’t known other people who tried this.</p>
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<p>If
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a person already has distinct cataracts, it might be worthwhile to experiment
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with a relatively high degree of hypercapnia, for example, breathing
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a 5% mixture of CO2 in air.</p>
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<p>Carbon
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dioxide, at higher levels than are normal at sea level, has a profound
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effect on free radicals, reducing the free radical activity in the blood
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to approximately zero, before reaching the level that produces acidosis.</p>
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<p>There
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are several situations in which carbon dioxide affects the hydration,
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water content, of biological materials, that I think give an insight
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into its effects on the lens. Hydrophilic glycoproteins are involved
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in each case. These are proteins with attached chains of sugar
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molecules that make them associate with a large amount of water.
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In the cornea, increased carbon dioxide strongly protects against swelling.
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The bulk of the cornea is a connective tissue that is relatively simple
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and passive compared to the compact cellular structure of the lens,
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and it is conventional to describe the thin layers of cells on the inside
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and outside of the cornea as being responsible for the water content
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of the underlying substance. However, even when the epithelial
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cells are removed, it has been demonstrated that carbon dioxide is able
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to prevent corneal swelling. (M.V. Riley, et al., “The roles of bicarbonate
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and CO2 in transendothelial fluid movement and control of corneal thickness," <em>
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Invest. Ophthalmol. Vis. Sci. 36(1),</em> 103-112, 1995.)</p>
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<p>Bronchial
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mucous secretions are an even simpler system, so it is very interesting
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that carbon dioxide is recognized as the most powerful regulator of
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their behavior. (This has important implications for “cystic
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fibrosis,” or mucoviscidosis.) Goodman and Gilman (page 1068, <em>
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Pharmacological Basis of Therapeutics,</em> 2nd Edition, Macmillan Co.,
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1956), say </p>
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<p>"Among
|
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inhalants, steam and carbon dioxide have been found to be excellent
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expectorants. Relative humidity above 85 per cent liquefies sputum,
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decreases its viscosity...." "Carbon dioxide is the
|
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most effective agent of all. It not only lowers the viscosity
|
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of tenacious sputum, thereby facilitating expectoration, but it decreases
|
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the volume of sputum by promoting its active resorption by bronchial
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mucosa." "A five to ten per cent concentration of carbon
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dioxide is adequate and well tolerated if administered at intervals."
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"Oxygen has been shown to be an antiexpectorant and has effects
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opposite to those of carbon"
|
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</p>
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<p>Oxygen
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tends to displace carbon dioxide from tissue, and is a source of free
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radicals.</p>
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<p>One
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of the best-known free radical scavenging substances that has been widely
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used as a drug is iodide.
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It has been used to treat asthma, parasites, syphilis, cancer, Graves’
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disease, periodontal disease, and arteriosclerosis. Diseases that
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produce tissue overgrowth associated with inflammation--granulomas--have
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been treated with iodides, and although the iodide doesn’t necessarily
|
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kill the germ, it does help to break down and remove the granuloma.
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Leprosy and syphilis were among the diseases involving granulomas* that
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were treated in this way. In the case of tuberculosis, it has
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been suggested that iodides combine with unsaturated fatty acids which
|
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inhibit proteolytic enzymes, and thus allow for the removal of the abnormal
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tissue. </p>
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<p>In
|
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experimental animals, iodide clearly delays the appearance of cataracts.
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(Buchberger, et al., 199l.)</p>
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<p>Inflammation,
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edema, and free radical production are closely linked, and are produced
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by most things that interfere with energy production.</p>
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<p>Endotoxin,
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produced by bacteria, mainly in the intestine, disrupts energy production,
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and promotes maladaptive inflammation. The wide spectrum of benefit
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that iodide has, especially in diseases with an inflammatory component,
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suggests first that it protects tissue by blocking free radical damage,
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but it also suggests the possibility that it might specifically protect
|
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against endotoxin. </p>
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<p>There
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are subtler differences in transparence that probably have a variety
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of causes, but differences in water content or hydration might be involved
|
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in the lower transparency that has been seen in women's lenses.
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Estrogen, which tends to produce edema and hypotonic body fluids, also
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increases prolactin production. Prolactin is involved in water
|
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and electrolyte regulation, and it has been found to <strong>accelerate the
|
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development of experimental cataracts.</strong> (M. C. Ng, et al, 1987.)
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These hormones are associated with the calcification of soft tissues,
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and cataracts contain very high levels of calcium. (Avarachan and Rawal,
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1987; Hightower and Reddy, 1982.)</p>
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<p>Estrogen
|
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is strongly associated with free radical processes, calcium mobilization,
|
||
and acetylcholine release, all of which are involved in the process
|
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of excitoxicity.
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Alvarez, et al., (1996) have shown a possible involvement of acetylcholine
|
||
in calcium mobilization in the lens.</p>
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<p>Serotonin
|
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is another regulatory substance strongly associated with prolactin and
|
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estrogen, and it also can be involved in disrupting the metabolism of
|
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the lens. This is one of the potential dangers in using supplemental
|
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tryptophan. (Candia, et al., 1980.) </p>
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<p>Old
|
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age commonly involves some changes in the color of tissues--loss of
|
||
pigment from hair and skin, with appearance of new pigment (age pigment,
|
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lipofuscin), which may appear as “liver spots.” But
|
||
there is also a tendency of the toenails, fingernails, teeth, and lenses
|
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to turn yellow or brown. Some of this dark material seems to be
|
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age pigment, derived from unsaturated fatty acids, but other components
|
||
have been identified, for example, tryptophan from damaged proteins.
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The Maillard reaction (similar to the browning that occurs in bread
|
||
crust) has often been mentioned in relation to aging, and involves the
|
||
combination of protein amino groups with sugars. But the browning
|
||
of the lens tends to be associated with the general age related drying
|
||
of the lens, it isn’t irregularly distributed, and it doesn’t significantly
|
||
harm vision.</p>
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<p>When
|
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I first heard about the age-related browning of the lens, I thought
|
||
that the experience of colors would be affected, so I devised a test
|
||
in which the relative darkness of blue and yellow could be judged in
|
||
comparison with a graded strip of shades of grey.</p>
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||
<p>After
|
||
people of ages ranging from 10 to 80 had given exactly the same matches,
|
||
I realized that the nervous system probably corrects for the “yellow
|
||
filter” effect of the brown lens.</p>
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||
<p>The
|
||
browning of tissues will be the subject of another newsletter.
|
||
</p>
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||
<p>Among
|
||
the interesting causes of cataracts<strong>: </strong>
|
||
Tamoxifen and hypotonic fluids, sodium deficiency<strong>;</strong> toxicity of tryptophan<strong>;</strong> oxidants (metals,
|
||
hydrogen peroxide, PUFA); diabetes, photosensitizers and sunlight<strong>; </strong>
|
||
|
||
excess calcium, deficient magnesium. Excess cortisol. Radiation.
|
||
Arachidonic and linoleic acids in other situations have been found to
|
||
block cells' regulation of their water content. Hypothyroidism
|
||
tends to increase the activity of serotonin, estrogen, prolactin, calcium,
|
||
and the tendency of tissues to retain water, and to decrease the level
|
||
of ATP.</p>
|
||
<p>Among
|
||
the factors that probably have a role in preventing cataracts<strong>: </strong>
|
||
Thyroid, progesterone, pregnenolone, vitamin E, iodide, pyruvate.
|
||
Increasing the carbon dioxide lowers the cell’s pH, and tends to resist
|
||
swelling. Palmitic acid (a saturated fat that can be synthesized
|
||
by our tissues) is normally oxidized by the lens. Calcium blockers
|
||
experimentally prevent cataracts, suggesting that magnesium and thyroid
|
||
(which also act to exclude calcium from cells) would have the same effect. </p>
|
||
<p>Thyroid
|
||
hormone is essential for maintaining adequate carbon dioxide production,
|
||
for minimizing lactic acid, cortisol and prolactin, for regulating calcium
|
||
and magnesium, for avoiding hypotonicity of the body fluids, and for
|
||
improving the ratio of palmitic acid to linoleic acid.</p>
|
||
<h2>References</h2>
|
||
<small>
|
||
<p>“Inhibition
|
||
of ionic transport and ATPase activities by serotonin analogues in the
|
||
isolated toad lens,” Candia OA; Lanzetta PA; Alvarez LJ; Gaines W,
|
||
Biochim Biophys Acta (602)2, 389-400, 1980. “Tryptamine, 5-methyltryptamine
|
||
and 5-methoxytryptamine had dual effects: 1 mM in the posterior bathing
|
||
solution depressed the potential difference of the posterior face of
|
||
the lens, which resulted in an increase in the translenticular potential
|
||
difference and short-circuit current; 1 mM in the anterior solution
|
||
(in contact with the lens epithelium) produced a quick and pronounced
|
||
reduction of the potential difference of the anterior face. This resulted
|
||
in a 90-100% decline of the translenticular short-circuit current. Serotonin
|
||
and tryptamine were then tested for their effect on the ATPases of lens
|
||
epithelium. Both amines inhibited the enzymes with tryptamine at 5 mM
|
||
completely inhibiting all ATPase activity. <strong>Since
|
||
tryptophan is transported from the aqueous humor into the lens and may
|
||
be converted by lens enzymes to serotonin and
|
||
tryptamine, these findings may have physiological implications in
|
||
cataractogenesis.”</strong> </p>
|
||
<p>“Effects
|
||
of Ca2+ on rabbit translens
|
||
short-circuit current: evidence for a Ca2+ inhibitable K+ conductance,"
|
||
Alvarez LJ; Candia OA; Zamudio AC, Curr Eye Res, 1996 Dec, 15:12, 1198-207.
|
||
PURPOSE: To characterize the effects of medium Ca2+ levels on rabbit
|
||
lens electrical properties. Overall, these results suggest that <strong>lens
|
||
Ca2(+)-mobilizing agents (e.g. acetylcholine)</strong> could trigger the
|
||
inhibition of epithelial K+ conductance(s) by the direct action of Ca2+
|
||
on K+ channels." </p>
|
||
|
||
<p>“Effects
|
||
of Ca2+ on rabbit translens short-circuit current: evidence for a Ca2+
|
||
inhibitable K+ conductance,” Alvarez LJ; Candia OA; Zamudio
|
||
AC, Curr Eye Res, 1996 Dec, 15:12, 1198-207. “PURPOSE: To characterize
|
||
the effects of medium Ca2+ levels on rabbit lens electrical properties.
|
||
Overall, these results suggest that lens Ca2(+)-mobilizing
|
||
agents (e.g. acetylcholine) could trigger the inhibition of epithelial
|
||
K+ conductance(s) by the direct action of Ca2+ on K+ channels.”
|
||
</p>
|
||
<p>“D600
|
||
increases the resistance associated with the equatorial potassium current
|
||
of the lens,” Walsh SP; Patterson JW, Exp Eye Res, 1992 Jul,
|
||
55:1, 81-5 “This effect is similar to that produced by quinine
|
||
and by a calcium-free medium, and is attributed to the prevention of
|
||
an increase in the calcium-dependent conductance produced by pCMPS.“
|
||
</p>
|
||
<p>“Effects
|
||
of hydrogen peroxide oxidation and calcium channel blockers on the equatorial
|
||
potassium current of the frog lens,” Walsh SP; Patterson JW, Exp Eye
|
||
Res, 1994 Mar, 58:3, 257-65. “Hydrogen peroxide, in concentrations
|
||
of 10-1000 microM, produces two major changes in the current-voltage
|
||
relationships associated with the equatorial potassium current of the
|
||
lens. First, the resting and reversal potentials become more negative
|
||
than they were prior to treatment with hydrogen peroxide and second,
|
||
the membrane resistance related to the equatorial current is decreased.
|
||
The shift in the resting and reversal potentials is in the opposite
|
||
direction from that produced by ouabain. Based on the Nernst equation,
|
||
the shift in the reversal potential suggests that there is an <strong>increase
|
||
in the concentration of potassium in the lens. The
|
||
86Rb uptake and efflux are increased. These observations suggest that
|
||
hydrogen peroxide stimulates the Na,K-pump. The decrease in membrane
|
||
resistance is inhibited by 100 microM of quinine, a calcium-dependent
|
||
potassium channel blocker, and does not decrease in a calcium-free medium.
|
||
This suggests that the decrease in resistance may be secondary to an
|
||
increase in lenticular calcium.</strong> These effects of hydrogen peroxide
|
||
are similar to those of p-chloromercuriphenylsulfonate
|
||
|
||
(pCMPS), a nearly impermeant sulfhydryl binding agent,<strong> and suggest
|
||
that permeant hydrogen peroxide may increase calcium influx by acting
|
||
on sulfhydryl groups on the outer surface of lens membranes.
|
||
Verapamil, a calcium channel blocker, is reported to prevent cataract
|
||
formation.</strong>” </p>
|
||
<p>“Effect
|
||
of prolactin on galactose cataractogenesis,” Ng MC; Tsui JY; Merola
|
||
LO; Unakar NJ phthalmic Res 19:2, 82-94, 1987. “Prolactin
|
||
has been known to affect the water and electrolyte balance. Because
|
||
increased lens hydration has been shown to be a common phenomenon in
|
||
most, if not all types of cataracts, we have been interested in investigating
|
||
a possible role of prolactin in sugar cataract induction and progression.
|
||
For this study, we have used morphological and biochemical approaches.
|
||
The prolactin delivery method involved intraperitoneal implantation
|
||
of one or more pellets in Sprague-Dawley female rats. Following implantation
|
||
of the desired number of prolactin or control (nonprolactin) pellets,
|
||
animals were either fed galactose and lab chow, or lab chow diet. Gross
|
||
morphological observations of whole lenses, slit-lamp examination of
|
||
lenses and light microscopic analysis of lens sections showed that in
|
||
the galactose-fed prolactin
|
||
group, galactose associated alteration progressed faster and total opacification
|
||
(mature cataract development) was achieved earlier than in the nonprolactin
|
||
group. The levels of galactose and dulcitol were higher in the lenses
|
||
of galactose-fed prolactin treated rats as compared to lenses from nonprolactin
|
||
(control) rats. No significant difference in lens Na+-K+ ATPase activity
|
||
between the prolactin and nonprolactin group was observed. Our results
|
||
indicate that prolactin accelerates galactose-induced cataractogenesis
|
||
in rats." </p>
|
||
<p>"A
|
||
hypothetical mechanism for toxic cataract due to oxidative damage to
|
||
the lens epithelial membrane," Bender CJ Med Hypotheses, 1994 Nov,
|
||
43:5, 307-11 Lenticular opacities can be induced by numerous external
|
||
agents that <strong>coincide with those that catalyze oxidative damage to
|
||
lipids. </strong>One of the consequences of lipid peroxidation is that the
|
||
affected membrane is rendered more permeable to protons. A proton leak
|
||
in the tight epithelium of lens <strong>would uncouple the
|
||
Na+/K(+)-ATPases that regulate the water</strong> and ionic content of the
|
||
bounded tissue. Once regulatory control of the osmotic pressure is lost, <strong>
|
||
|
||
the phase state of the</strong> cell's soluble proteins would change, <strong>
|
||
leading to refractive changes or, in extreme cases, precipitation</strong>.
|
||
The same does not occur in cornea because the stroma is an extracellular
|
||
polymer blend rather than solution of soluble polymers. Polymeric phase
|
||
transitions in the cornea require that divalent cations pass the epithelial
|
||
membrane, which can occur only through the action of ionophores.
|
||
</p>
|
||
<p>Tsubota
|
||
K; Laing RA; Kenyon KR Invest Ophthalmol Vis Sci, 1987 May, 28:5,
|
||
785-9, <strong>Abnormalities in glucose metabolism are thought to be among
|
||
the main causes of cataract formation. </strong>
|
||
The authors have made noninvasive biochemical measurements of the lens
|
||
that provide information concerning glucose metabolism in the lens epithelium.
|
||
The autofluorescence of reduced pyridine nucleotides (PN) and oxidized
|
||
flavoproteins (Fp) within the rabbit lens were noninvasively measured
|
||
as a function of depth using redox fluorometry. The peak of the autofluorescence
|
||
at 440 nm (excited at 360 nm) and 540 nm <strong>(excited at 460
|
||
nm) were determined at the lens epithelium. When 8
|
||
mM sodium pentobarbital, a known inhibitor of
|
||
mitochondrial respiration, was applied to the lens, the
|
||
autofluorescence peak at 440 nm increased and that at 540 </strong><strong>nm decreased. The 440
|
||
nm autofluorescence is thought to be from </strong>
|
||
|
||
reduced pyridine nucleotides, whereas the 540 nm autofluorescence is
|
||
from the oxidized flavoprotein. Blocking lens respiration with pentobarbital
|
||
caused an increase in the PN/Fp ratio by a factor of 3 within 3.5 hr
|
||
after pentobarbital application.” </p>
|
||
<p>[Use
|
||
of pyrimidine bases and ATP for conservative treatment of early cataracts]
|
||
Larionov LN Oftalmol Zh, 1977, 32:3, 221-2
|
||
</p>
|
||
<p>“Concentrations
|
||
of some ribonucleotides, L-lactate, and pyruvate in human senile cataractous
|
||
lenses with special reference to anterior capsular/subcapsular opacity,”
|
||
Laursen AB Acta Ophthalmol (Copenh), 1976 Dec, 54:6, 677-92 The concentrations
|
||
of some ribonucleoside tri- and diphosphates, adenosine-5'-monophosphate,
|
||
L-lactate and pyruvate were determined in human senile cataractous lenses
|
||
removed during cataract operations. Pyruvate concentrations were found
|
||
to be negligible (median = 56 mumol/kg lens wet weight) in 15 human
|
||
senile cataractous lenses. On the basis of correlations between the
|
||
biomicroscopic appearances of the senile cataractous lenses (N = 80)
|
||
and the concentrations and ratios of the metabolites in question, the
|
||
following classification was found to be justified: 1. Immature cataractous
|
||
lenses without anterior capsular/subcapsular opacity: high levels of
|
||
ribonucleoside triphosphates (RTP), high sums of RTP, ribonucleoside
|
||
diphosphates (RDP), and adenosine 5'-monophosphate (AMP) as well as <strong>
|
||
high levels of L-lactate and high ratios of
|
||
L-lactate in the lens/L-lactate in the aqueous</strong>. 2. Immature cataractous
|
||
lenses with anterior capsular/subcapsular opacity; intermediate levels
|
||
of RTP, intermediate values for the sums of RTP, RDP, and AMP, <strong>high
|
||
L-lactate levels, and intermediate values of the ratios of
|
||
L-lactate in the lens/L-lactate in the aqueous.</strong>”
|
||
|
||
</p>
|
||
<p>Sulochana
|
||
KN; Ramakrishnan S; Vasanthi SB; Madhavan HN; Arunagiri K; Punitham
|
||
R, “First report of congenital or infantile cataract in deranged proteoglycan
|
||
metabolism with released xylose,” Br J Ophthalmol, 1997 Apr, 81:4,
|
||
319-23." "Of 220 children of both sexes below
|
||
12 years of age, with congenital or infantile cataract treated in Sankara
|
||
Nethralaya, Madras, India, during a period of 2 years, 145 excreted
|
||
fragments of GAG (heparan and chondroitin sulphates) in their urine.
|
||
There was no such excretion among the control group of 50 children. <strong>
|
||
The same was found accumulated in the blood and lenses of affected children.</strong>
|
||
In addition, xylose was present in small amounts in the urine and blood
|
||
and xylitol was present in the lens. There was a significant elevation
|
||
in the <strong>activity of beta glucuronidase in lymphocytes and urine,</strong>
|
||
when compared with normals.
|
||
All the above findings suggest deranged proteoglycan metabolism. As
|
||
the urine contained mostly GAG fragments and very little xylose, Benedict's
|
||
reagent was not reduced. This ruled out galactosaemia.CONCLUSION: An
|
||
increase of <strong>beta glucuronidase activity might have caused extensive
|
||
fragmentation of GAG</strong> with resultant accumulation in the blood and
|
||
lens and excretion in urine. Small amounts of xylose may have come from
|
||
xylose links between GAG and core protein of proteoglycans. Owing to
|
||
their polyanionic nature, GAG fragments in the lens might abstract
|
||
sodium, and with it water, thereby increasing the hydration of the lens.
|
||
Excessive hydration and the osmotic effect of xylitol from xylose might
|
||
cause cataract. While corneal clouding has been reported in inborn acid
|
||
mucopolysaccharidosis, congenital or infantile cataract with deranged
|
||
metabolism of proteoglycans (acid mucopolysaccharide-xylose-protein
|
||
complex) is reported in children for the first time."
|
||
|
||
</p>
|
||
<p>"State
|
||
of electrolytes, osmotic balance and the activity of ATPase in the lenses
|
||
of selenite--induced cataracts," Avarachan PJ; Rawal UM Indian
|
||
J Ophthalmol, 1987, 35:5-6, 210-3. "Selenite-cataracts incorporated
|
||
many morphological characteristics observed in human senile catracts.
|
||
Progressive elevation of sodium, marked loss of potassium, <strong>several
|
||
fold increment of calcium; considerable loss of magnesium levels,</strong>
|
||
a dose-response reduction of total-ATPase activity <strong>and significant
|
||
hydration are the important features</strong> observed in the lens during
|
||
the progressive treatment of selenite.
|
||
The sodium-potassium imbalance is found to be a secondary effect during
|
||
the development of cataract and is suggested to bring about by <strong>an
|
||
abnormal accumulation of calcium ions</strong> and inactivation of transport
|
||
enzyme. The calcium activated proteases could be the promoting factor
|
||
for the proteolysis and insolubilization of lens proteins in the inducement
|
||
of selenite cataract. The impact of selenite on the SH containing ATPase
|
||
anzymes could be the cause of impairment in energy metabolism, derangement
|
||
of electrolytes and osmotic imbalance which, in turn, accelerate the
|
||
cortical involvement of lens opacities." </p>
|
||
|
||
<p>"Glucose
|
||
metabolism by human cataracts in culture," Wolfe JK; Chylack
|
||
LT Jr Exp Eye Res 43:2, 243-9, 1986. “Metabolism in human senile cataracts
|
||
has been studied using uniformly labeled [14C]glucose. Intracapsularly
|
||
extracted lenses were cultured in TC-199 media with a glucose concentration
|
||
of 5.5 mM. Results show that lactate production accounts for 97% of
|
||
the glucose metabolized. Under these standard incubation conditions
|
||
there is negligible accumulation of alpha-glycerol phosphate, glucose-6-phosphate,
|
||
and sorbitol. The rate of lactate production was found to be relatively
|
||
uniform over a range of cataract severities which were determined from
|
||
the CCRG classification. The effects of several perturbants in the medium
|
||
were measured.<strong> An ATP concentration of 3
|
||
mM was found to inhibit lactate production." </strong>
|
||
</p>
|
||
<p>M.
|
||
V. Riley, et al., "The roles of bicarbonate and CO2 in transendothelial
|
||
fluid movement and control of corneal thickness," Invest. Ophthalmol.
|
||
Vis. Sci. 36(1), 103-112, 1995. <strong>"The equilibrium thickness
|
||
of deepithelialized corneas swollen with
|
||
HCO-/CO2 on both surfaces was 35 microns less than that of corneas swollen
|
||
in HPO4-." "Normal corneal thickness can be maintained
|
||
in vitro only in media that contain
|
||
HCO3- at concentrations of more than 20
|
||
mM."</strong> </p>
|
||
|
||
<p>"The
|
||
effect of X-irradiation on the sodium-potassium-activated adenosine
|
||
triphosphatase (Na-K-ATPase) activity in the epithelium of the rat lens.
|
||
A histochemical and biochemical study," Palva M Acta Ophthalmol
|
||
(Copenh), 1978 Jun, 56:3, 431-8. "The epithelial Na-K-ATPase
|
||
activity of the rat lens was studied after X-irradiation at intervals
|
||
of three to ninety days. The enzyme was demonstrated histochemically
|
||
by light microscopy and it was measured biochemically by a fluorometric
|
||
method. Neither histochemical nor biochemical changes of Na-K-ATPase
|
||
content of the lens epithelium were observed during the development
|
||
of cataract. In whole-mount preparations the enzyme activity was localized
|
||
in the cell membranes. However, one month after radiation a few peripheral
|
||
cells had in addition a precipitated over the whole cell. <strong>The unaltered
|
||
Na-K-ATPase</strong><strong> content
|
||
in the epithelium</strong> suggests that the hydration of the lens after
|
||
X-irradiation is primarily caused by <strong>changes in the passive permeability
|
||
properties of the cell membranes and not by a decreased capacity of
|
||
the activity cation pump." </strong> </p>
|
||
<p>McNamara
|
||
NA; Polse KA; Bonanno JA<strong> “Stromal acidosis modulates corneal swelling.” </strong>
|
||
|
||
Invest Ophthalmol Vis Sci, 1994 Mar, 35:3, 846-50 "PURPOSE. Studies
|
||
have shown that stromal acidosis reduces the rate of corneal thickness
|
||
recovery after induced edema, providing the first human in vivo evidence
|
||
that corneal pH can influence corneal hydration control. This finding
|
||
raises the question of the possible effect that pH may have on induced
|
||
corneal swelling. To explore this question, the corneal swelling response
|
||
to hypoxia was measured while stromal pH was controlled. METHODS. Corneal
|
||
edema and stromal acidosis was induced in ten subjects by passing a
|
||
mixture of nitrogen and carbon dioxide gas across the eyes through tight-fitting
|
||
goggles. <strong>One eye of each subject received 100% N2, whereas the
|
||
contralateral eye received a mixture of 95% N2 and 5%
|
||
CO2. Exposures of 95% N2 + 5% CO2 lower pH on average to 7.16 versus
|
||
7.34 for 100% N2 alone.</strong> Before and after 2.5 hours of gas exposure,
|
||
central corneal thickness (CCT) was measured. RESULTS. <strong>Eyes exposed
|
||
to the lower pH environment (eg, N2 +
|
||
CO2) developed less change in CCT</strong> compared to the eyes receiving
|
||
N2 alone. Overall increase in CCT was 29.9 +/- 5.3 microns for eyes
|
||
exposed to the 95% N2 + 5% CO2 gas mixture, versus 37.1 +/- 4.8 microns
|
||
for 100% N2 <strong>eyes (P < 0.0001). CONCLUSIONS. The corneal swelling
|
||
response to hypoxia can be reduced by lowering
|
||
stromal pH. Because changes in corneal pH alone have not been found
|
||
to alter steady-state CCT, it is proposed that pH </strong>
|
||
exerts its effect only under non-steady-state conditions (ie, corneal
|
||
swelling and deswelling). This suggests that acidosis may produce changes
|
||
in the <strong>rate of lactate metabolism</strong> or alter endothelial hydraulic
|
||
conductivity." </p>
|
||
|
||
<p>Buchberger
|
||
W; Winkler R; Moser M; Rieger G, "Influence of iodide on cataractogenesis
|
||
in Emory mice," Ophthalmic Res, 1991, 23:6, 303-8. Cataract
|
||
development was studied in two groups of Emory mice by periodical biomicroscopic
|
||
examinations (beginning at 5 weeks of age) and by a final evaluation
|
||
of water-soluble SH groups in the lenses. The experimental group was
|
||
given 256 micrograms iodide/kg body weight with the drinking water throughout
|
||
the study. The untreated control group received tap water. <strong>Iodide
|
||
treatment induced a delay of cataract formation...."</strong> "A
|
||
still significant difference in the degree of cataract was also found
|
||
between the two groups at week 47 of age. No difference was found in
|
||
the content of water-soluble SH groups. The results are discussed in
|
||
relation <strong>to the known antioxidant and .OH-scavenging effect of iodide
|
||
and to the oxidative changes in the lens occurring during progression
|
||
of cataract development.</strong>" </p>
|
||
<p>"[The
|
||
chemical nature of the fluorescing products accumulating in the lipids
|
||
of the crystalline lenses of mice with hereditary cataract]," Shvedova
|
||
AA; Platonov ES; Polianskii NB; Babizhaev
|
||
MA; Kagan VE Biull Eksp Biol Med, 1987 Mar, 103:3, 301-4.<strong> "The
|
||
content of diene conjugates (lipid
|
||
hydroperoxides) was shown to be significantly higher in lipids extracted
|
||
from the lenses of mice with hereditary cataract than in the controls.
|
||
The same holds true for characteristics of fluorescence of the end-product
|
||
of lipid peroxidation."</strong> "It was established that high-molecular
|
||
weight fluorescent fractions corresponded to lipid components of <strong>
|
||
|
||
lipofuscin-like pigments.</strong> NMR and mass spectrometry of low-molecular
|
||
weight fractions suggested that they contained predominantly products
|
||
of free radical oxidation of <strong>long chain polyunsaturated fatty acids
|
||
(C22:6). "</strong> </p>
|
||
<p>"Formation
|
||
of N'-formylkynurenine in proteins from lens and other sources by exposure
|
||
to sunlight," Pirie A Biochem J, 1971 Nov, 125:1, 203-8.
|
||
</p>
|
||
<p>"Lipid
|
||
fluorophores of the human crystalline lens with cataract."
|
||
Babizhayev MA Graefes Arch Clin Exp Ophthalmol, 1989, 227:4, 384-91
|
||
"It has been established that the development of cataract is accompanied
|
||
by the formation of various fluorophores in the lipid fraction of the
|
||
lens. These lipid-fluorescing products have been separated chromatographically
|
||
according to polarity and molecular weight. It is shown that the
|
||
initial stages of the development of cataract are characterized by the
|
||
appearance of lipid fluorophores in the near ultraviolet and violet
|
||
regions of the spectrum <strong>(excitation maximum 302-330
|
||
nm, emission maximum 411 nm) with low</strong> polarity and a small molecular
|
||
weight; the maturing of the cataract is<strong> characterized by an increase
|
||
in the intensity of the long-wave fluorescence of the lipids in the
|
||
blue-green region (430-480 nm) and by the formation of </strong>
|
||
|
||
polymeric high-molecular-weight fluorescing lipid products with high
|
||
polarity. It has been demonstrated that the appearance of lipid fluorophores
|
||
in the <strong>crystalline lens is associated with the free radical oxidative
|
||
modification of the phospholipids and fatty acids in cataract." </strong>
|
||
</p>
|
||
<p>"Incidence
|
||
of cataracts in the mobile eye hospitals of Nepal," Brandt F; Malla
|
||
OK; Pradhan YM; Prasad LN; Rai NC; Pokharel RP; Lakhe S, Graefes Arch
|
||
Clin Exp Ophthalmol, 1982, 218:1, 25-7 The incidence of cataract in
|
||
Nepal was determined from data collected in 14 mobile eye hospitals
|
||
(called 'eye camps'). Of a total of <strong>12,217</strong> patients examined
|
||
in the out-patient department (OPD), cataract surgery was performed
|
||
on 2,163. The percentage of cataract patients in the OPD was <strong>less
|
||
in the mountains (13.8%) than in the
|
||
Tarai plains (19.8%).</strong>
|
||
In the inhabitants of the mountains, the majority of whom belong to
|
||
the Tibeto-Birman race, <strong>cataracts appeared at a significantly later
|
||
age in both males and females compared to the people of the plains,
|
||
who are mostly Indo-Aryan.</strong> Cataracts were discovered in both groups
|
||
at a younger age in women than in men." </p>
|
||
|
||
<p>"Associations
|
||
among cataract prevalence, sunlight hours, and altitude in the Himalayas."
|
||
Brilliant LB; Grasset NC; Pokhrel RP; Kolstad A; Lepkowski JM; Brilliant
|
||
GE; Hawks WN; Pararajasegaram R., Am J Epidemiol 118:2, 250-64
|
||
1983. "The relationship between cataract prevalence, altitude,
|
||
and sunlight hours was investigated in a <strong>large national probability
|
||
sample survey of 105 sites</strong> in the Himalayan kingdom of Nepal, December
|
||
1980 through April 1981. Cataract of senile or unknown etiology was
|
||
diagnosed by ophthalmologists in 873 of <strong>30,565</strong> <strong>full-time
|
||
life-long residents</strong> of survey sites. Simultaneously, the altitude
|
||
of sites was measured using a standard mountain altimeter. Seasonally
|
||
adjusted average daily duration of sunlight exposure for each site was
|
||
calculated by a method which took into account latitude and obstructions
|
||
along the skyline. Age- and sex-standardized <strong>cataract prevalence
|
||
was 2.7 times higher in sites at an altitude of 185 meters or less than
|
||
in sites over 1000 meters. Cataract prevalence was negatively correlated
|
||
with altitude</strong> (r = -0.533, p less than 0.0001). However, a positive
|
||
correlation between cataract prevalence and sunlight was observed (r
|
||
= 0.563, p less than 0.0001). Sites with an average of 12 hours of sunlight
|
||
exposure had 3.8 times as much cataract as sites with an average of
|
||
only seven hours of exposure. Sunlight was blocked from reaching certain
|
||
high altitude sites by tall neighboring mountains. "
|
||
|
||
</p>
|
||
<p><strong>"The
|
||
untenability of the sunlight hypothesis of
|
||
cataractogenesis</strong>," Harding JJ Doc Ophthalmol 88:3-4, 345-9,
|
||
1994-95. "The excess prevalence of cataract in <strong>third world
|
||
countries led early this century to the hypothesis that sunlight causes
|
||
cataract. The hypothesis, which ignored differences in diet, culture,
|
||
poverty and prevalence of other diseases</strong> such as diarrhoea, received
|
||
little support until about thirty years ago when biochemical studies
|
||
were set up to explore the browning of lens proteins, which is a common
|
||
feature of cataract on the Indian subcontinent. Initially these studies
|
||
were encouraging in that exposure to sunlight caused some changes seen
|
||
in cataractous lenses, but eventually the hypothesis was rejected because
|
||
the first change in the laboratory was the destruction of tryptophan, <strong>but this was not found
|
||
in brown cataract lenses.</strong> A brown nuclear cataract could not be
|
||
produced artificially in the laboratory using sunlight or UV exposure.
|
||
Exposure of laboratory animals has produced lens opacities, but in most
|
||
experiments the doses required have also caused keratitis, conjunctivitis,
|
||
iritis and inflammation. The cornea seems more sensitive than the lens,
|
||
which is not surprising, as it gets the first chance to absorb damaging
|
||
UV. The biochemical rejection of the hypothesis coincided with the re-start
|
||
of the epidemiological studies. Most of these are simply latitude studies
|
||
and are no more than a repeat of what was available sixty years ago.
|
||
They do not help to find a cause. <strong>Two studies showed that cataract
|
||
was less common at higher altitude in the Himalayas, but unfortunately
|
||
led to opposing conclusions</strong>. On the basis of common knowledge that
|
||
UV exposure was greater at higher altitude, the first altitude study
|
||
led to the rejection of the sunlight hypothesis."
|
||
|
||
</p>
|
||
<p>"Anticataract
|
||
action of vitamin E: its estimation using an in vitro steroid cataract
|
||
model," Ohta Y; Okada H; Majima Y; Ishiguro I Ophthalmic
|
||
Res, 1996, 28 Suppl 2:, 16-25 “The aim of this study was to
|
||
estimate the anticataract action of vitamin E using an in vitro methylprednisolone
|
||
(MP)-induced cataract model. The same severity of early cortical cataract
|
||
was induced in lenses isolated from male Wistar rats aged 6 weeks by
|
||
incubation with MP (1.5 mg/ml) in TC-199 medium. The cataractous lenses
|
||
showed slight increases in lipid peroxide (LPO) content and Na+/K+ ratio
|
||
and slight decreases in reduced glutathione (GSH) content and glyceraldehyde-3-phosphate
|
||
dehydrogenase (GAP-DH), a sensitive index of oxidative stress, and Na+,K(+)-ATPase
|
||
activities. When the cataractous lenses were further incubated in TC-199
|
||
medium with and without vitamin E (250 micrograms/ml) for 48 h, the
|
||
progression of cataract was prevented in the vitamin E-treated lenses, but not in the vitamin E-untreated
|
||
lenses. The vitamin E-untreated lenses showed a decrease in vitamin
|
||
E content and an increase in water content in addition to further increases
|
||
in LPO content and Na+/K+ ratio and further decreases in GSH content
|
||
and GAP-DH and Na+,K(+)-ATPase activities. In contrast, the changes
|
||
of these components and enzymes except for GSH were attenuated in the
|
||
vitamin E-treated lenses. From these results, it can be estimated that
|
||
vitamin E prevents in vitro cataractogenesis in rat lenses treated with
|
||
MP by protecting the lenses against oxidative damage and loss of membrane
|
||
function. " </p>
|
||
<p>"Prevention
|
||
of oxidative damage to rat lens by pyruvate in vitro: possible attenuation
|
||
in vivo," Varma SD; Ramachandran S; Devamanoharan PS; Morris SM;
|
||
Ali AH,.Curr Eye Res, 1995 Aug, 14:8, 643-9 “Studies have been
|
||
conducted to assess the possible preventive effect of pyruvate against
|
||
lens protein oxidation and consequent denaturation and insolubilization.
|
||
Rat lens organ culture system was used for these studies. The content
|
||
of water insoluble proteins (urea soluble) increased if the lenses were
|
||
cultured in medium containing hydrogen peroxide. Incorporation of pyruvate
|
||
in the medium prevented such insolubilization. The insolubilization
|
||
was associated primarily with loss of gamma crystallin fraction of the
|
||
soluble proteins. PAGE analysis demonstrated that insolubilization is related to -S-S- bond formation
|
||
which was preventable by pyruvate. Since pyruvate is a normal tissue
|
||
metabolite the findings are considered pathophysiologically significant
|
||
against cataract formation. This was apparent by the <strong>prevention of
|
||
selenite cataract in vivo by intraperitoneal administration of
|
||
pyruvate.</strong>” </p>
|
||
|
||
<p>"Glucocorticoid-induced
|
||
cataract in chick embryo monitored by Raman spectroscopy," Mizuno
|
||
A; Nishigori H; Iwatsuru M Invest Ophthalmol Vis Sci, 30:1, 132-7, 1989.
|
||
“Glucocorticoid-induced cataract lens in chick embryo was monitored
|
||
by laser Raman spectroscopy. The lens opacity that appeared in chick
|
||
embryo is a reversible one. Raman spectra show no significant change
|
||
in the relative content of water or secondary structure of the proteins
|
||
upon lens opacification. The intensity ratios of tyrosine doublet bands
|
||
in Raman spectra between clear and opaque lens portions are changes. <strong>
|
||
This change is reversible, </strong>and <strong>is interpreted as a protein-water
|
||
phase separation that occurred during lens
|
||
opacification</strong>.” </p>
|
||
<p>“[NMR
|
||
study of the state of water in the human lens during cataract development]”
|
||
Babizhaev MA; Deev AI; Nikolaev GM, Biofizika 30:4, 671-4,1985. “Water
|
||
proton spin-spin relaxation times (T2) and the content of bound, "non-freezable"
|
||
at -9 degrees C water in both normal human lenses and human lenses of
|
||
different stages of cataract progression (cataracta incipiens, nondum
|
||
matura, mature hypermatura) were measured by NMR spin echoes method.
|
||
By the stage of cataracta nondum matura, increase of bound water content
|
||
and simultaneous, almost half decrease of the relaxation time (T2),
|
||
were observed. However, on the following stages of cataract evaluation
|
||
(almost mature, mature cataracts) <strong>a gradual decrease of bound water
|
||
content is noted, </strong>but only for the mature cataract stage the water
|
||
content significantly differs from that of the normal one. On the stage
|
||
of hypermature cataract the presence of two unexchanged with each other
|
||
fractions of water is found. The obtained data are <strong>explained by lens
|
||
protein reconstructions during the cataract progression.</strong>”
|
||
|
||
</p>
|
||
<p>Hightower
|
||
KR; Reddy VN “Ca++-induced cataract.” Invest Ophthalmol Vis Sci,
|
||
1982 Feb, 22:2, 263-7 “Cataracts in cultured rabbit lenses were produced
|
||
by elevation of internal calcium. Experimental procedures were successful
|
||
in increasing levels of total and bound Ca++, often without significant
|
||
changes in sodium, potassium, or water content. Although the excess
|
||
in calcium was predominantly associated with water-soluble proteins
|
||
and was freely diffusible, a significant amount was bound to membranes
|
||
and cytosol water-insoluble proteins. Thus, in lenses with a 10-fold
|
||
increase in total Ca++, the bound Ca++ increased twofold, nearly 35%
|
||
of which remained fixed to water-insoluble and membrane proteins after
|
||
exhaustive (72 hr) dialysis. In contrast, over 95% of the Ca++ in water-soluble
|
||
protein fractions was removed by dialysis.” </p>
|
||
<p>[Use
|
||
of pyrimidine bases and ATP for conservative treatment of early cataracts]
|
||
Larionov LN Oftalmol Zh, 1977, 32:3, 221-2. </p>
|
||
<p>"Noninvasive
|
||
measurements of pyridine nucleotide and flavoprotein in the lens,"
|
||
Tsubota K; Laing RA; Kenyon KR Invest Ophthalmol Vis Sci 28:5, 785-9,
|
||
1987. "<strong>Abnormalities in glucose metabolism are thought to be
|
||
among the main causes of cataract formation. </strong>
|
||
The authors have made noninvasive biochemical measurements of the lens
|
||
that provide information concerning glucose metabolism in the lens epithelium.
|
||
The autofluorescence of reduced pyridine nucleotides (PN) and oxidized
|
||
flavoproteins (Fp) within the rabbit lens were noninvasively measured
|
||
as a function of depth using redox fluorometry. The peak of the autofluorescence
|
||
at 440 nm (excited at 360 nm) and 540 nm <strong>(excited at 460
|
||
nm) were determined at the lens epithelium. When 8
|
||
mM sodium pentobarbital, a known inhibitor of
|
||
mitochondrial respiration, was applied to the lens, the
|
||
autofluorescence peak at 440 nm increased and that at 540
|
||
nm decreased. The 440 nm autofluorescence is thought to be from </strong>
|
||
|
||
reduced pyridine nucleotides, whereas the 540 nm autofluorescence is
|
||
from the oxidized flavoprotein. Blocking lens respiration with pentobarbital
|
||
caused an increase in the PN/Fp ratio by a factor of 3 within 3.5 hr
|
||
after pentobarbital application." </p>
|
||
<p>"Concentrations
|
||
of some ribonucleotides, L-lactate, and pyruvate in human senile cataractous
|
||
lenses with special reference to anterior capsular/subcapsular opacity,"
|
||
Laursen AB Acta Ophthalmol (Copenh) 54:6, 677-92,1976. “The concentrations
|
||
of some ribonucleoside tri- and diphosphates, adenosine-5'-monophosphate,
|
||
L-lactate and pyruvate were determined in human senile cataractous lenses
|
||
removed during cataract operations. Pyruvate concentrations were found
|
||
to be negligible (median = 56 mumol/kg lens wet weight) in 15 human
|
||
senile cataractous lenses. On the basis of correlations between the
|
||
biomicroscopic appearances of the senile cataractous lenses (N = 80)
|
||
and the concentrations and ratios of the metabolites in question, the
|
||
following classification was found to be justified: 1. Immature cataractous
|
||
lenses without anterior capsular/subcapsular opacity: high levels of
|
||
ribonucleoside triphosphates (RTP), high sums of RTP, ribonucleoside
|
||
diphosphates (RDP), and adenosine 5'-monophosphate (AMP) as well as <strong>
|
||
high levels of L-lactate and high ratios of
|
||
L-lactate in the lens/L-lactate in the aqueous</strong>. 2. Immature cataractous
|
||
lenses with anterior capsular/subcapsular opacity; intermediate levels
|
||
of RTP, intermediate values for the sums of RTP, RDP, and AMP, <strong>high
|
||
L-lactate levels, and intermediate values of the ratios of
|
||
L-lactate in the lens/L-lactate in the aqueous."</strong>
|
||
</p>
|
||
<p>"Lipid
|
||
fluorophores of the human crystalline lens with cataract," Babizhayev
|
||
MA Graefes Arch Clin Exp Ophthalmol, 1989, 227:4, 384-91. [Initial
|
||
stages of cataracts are characterized by the fluorescence of the products
|
||
of fatty acid free radical oxidation.] </p>
|
||
</small>
|
||
<hr>
|
||
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