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The transparency of life: Cataracts as a model of age-related disease

生命的透明度:白内障是年龄相关疾病的典范

by Raymond Peat

Cataracts can disappear when the eye's metabolic condition is corrected. A supply of energy is essential to maintain the transparent structure.

Lactic acid increases as carbon dioxide decreases, during a typical energy deficiency. Deficient thyroid, and the resulting excess of cortisol relative to pregnenolone and progesterone, define the energy deficiency.

Increased lactate relative to CO2 in the cell alters cell pH and electrical charge, causing swelling. Swelling and increased water content characterize the cataract.

High altitude is inversely related to cataracts, despite the known role of sunlight in causing cataracts; this is a strong confirmation of the protective role of carbon dioxide.

当眼睛的新陈代谢状况得到纠正时,白内障就会消失。能源的供应对于维持透明的结构至关重要。

在典型的能量缺乏期间,乳酸随着二氧化碳的减少而增加。缺乏甲状腺,以及由此导致的皮质醇相对于孕烯醇酮和孕酮过量,是能量缺乏的定义。

细胞内乳酸相对于CO2的增加改变了细胞的pH值和电荷,导致细胞肿胀。肿胀和含水量增加是白内障的特征。

高海拔与白内障的关系是相反的,尽管众所周知阳光会导致白内障;这有力地证实了二氧化碳的保护作用。

In the markets around Lake Patzcuaro, they sell green transparent fish, about 6 inches long. When cooked, the meat is white, like ordinary fish. Most fish filets are a little translucent, but are at least cloudy, and usually pink by transmitted light. I don’t know how the transparent fish work, because it seems that the blood and the network of blood vessels needed to sustain muscle activity would diffuse the light. Anyway, cooking disrupts the mysteriously ordered state of water and proteins that makes them transparent, roughly the way egg-white loses its transparency when it is cooked. I have never heard a convincing explanation for the opacity of cooked egg-white, either, but anything that disrupts the original structuring of the protein-water interaction will destroy the transparency.

在帕茨库罗湖周围的市场上,人们出售绿色透明的鱼,大约6英寸长。煮熟后,肉是白色的,像普通的鱼。大多数鱼片是半透明的,但至少是浑浊的,在透射光下通常是粉红色的。我不知道这种透明的鱼是如何工作的,因为似乎血液和维持肌肉活动所需的血管网络会散射光线。总之,烹饪破坏了水和蛋白质的神秘有序状态,使它们变得透明,大致就像蛋清在烹饪时失去透明度一样。对于煮熟的蛋清的不透明,我也从来没有听到过一个令人信服的解释,但任何破坏蛋白质-水相互作用的原始结构的东西都会破坏透明度。

Around 1970, I used a technique called nuclear magnetic resonance (NMR), which is the basis for the procedure known as MRI (magnetic resonance imaging), to compare the state of water in old (uterine) tissue and young tissue. Old tissue predictably contains less water than young tissue, but I found that the water in the old tissue was in a relatively free and uncontrolled state. When tissue swells and takes up water, more of the water is likely to be in this uncontrolled state, and this is one of the things that makes MRI so useful, because tumors, for example, show up vividly because of their large amount of uncontrolled (“unbound”) water. I suspect that the measurements I made on uterine tissue showed a localized effect, that opposed the general trend toward increased dryness with aging. In the case of cataracts, this is clearly the case: Most of the lens becomes drier with age, but at a certain point there is a reversal, and some of the tissue takes up too much water. That’s why I refer to cataracts as a model of age-related disease, rather than as a model of aging. In this sense, I am including them among the inflammatory diseases of aging–colitis, arthritis, and cancer, for example. MRI now can show developing cataracts before they are visible, because of increased water content in the area.

大约在1970年,我使用了一种叫做核磁共振(NMR)的技术,这是核磁共振成像(MRI)程序的基础,来比较年老(子宫)组织和年轻组织中的水的状态。可以预见,旧的组织比年轻的组织含有更少的水,但我发现旧组织中的水处于一种相对自由和不受控制的状态。当组织膨胀并吸收水分时,更多的水可能处于这种不受控制的状态,这是核磁共振成像如此有用的原因之一,因为以肿瘤为例,由于其大量不受控制的(“未结合的”)水,所以能生动地显示出来。我怀疑我对子宫组织所做的测量显示了一种局部效应,这与随着年龄增长而干燥的普遍趋势相反。就白内障而言,情况很明显:随着年龄的增长,大多数晶状体变得干燥,但在某个点上出现逆转,一些组织吸收了过多的水分。这就是为什么我说白内障是年龄相关疾病的模型,而不是衰老的模型。从这个意义上说,我把它们包括在衰老引起的炎症疾病中,例如结肠炎、关节炎和癌症。现在,由于该地区的含水量增加,核磁共振成像可以在白内障出现之前就显示出来。

The lens of the eye is a fairly dense, tough, transparent living structure, which can develop opaque areas, cataracts, as a result of old age, poisoning, radiation, disease, or trauma. The varieties of cataract relate to the causes. Most of the oxidative metabolism of the lens is in or near the epithelial layer that surrounds it. Old-age cataracts most often begin in this region.

眼睛的晶状体是一种相当致密、坚硬、透明的活体结构,由于年老、中毒、辐射、疾病或创伤,它会形成不透明区域,如白内障。白内障的种类与病因有关。晶状体的大部分氧化代谢发生在其周围的上皮层内或附近。老年白内障最常发生在这个地区。

Although the efficient oxidative energy metabolism occurs near the surface of the lens, there is a constant flow of fluid through the lens, entering it mainly in the front and back, and leaving on its “sides” or equator (considering the front and back as the poles, the direction light passes through). Oxygen and nutrients are supplied to the lens by way of this circulation of fluid, entering mostly from the aqueous humor in front (which also supplies the cornea), but also from the vitreous humor behind the lens.

虽然高效氧化能量代谢发生在透镜表面附近,有一个恒流的流体通过镜头,进入主要集中在正面和背面,使其“双方”或赤道(考虑到前后的波兰人,方向光穿过)。氧气和营养物质通过这种液体循环供给晶状体,主要从晶状体前面的房水(也供给角膜)进入,但也从晶状体后面的玻璃体进入。

When the flow of nutrients and energy is impaired, the organized state of the protein and water system in the cell is damaged, and an excess of water is taken up by the cells, as the protein content decreases. The loss of organization causes light to be dispersed, with a loss of transparency.

当营养物质和能量的流动受到破坏时,细胞中的蛋白质和水系统的组织状态就会受到破坏,蛋白质含量下降时,细胞就会吸收多余的水分。组织的丧失导致光的分散,失去透明度。

The lens of the eye is usually treated as something so specialized that it is hardly considered to be part of our living substance, just as dentistry has tended to treat teeth as inert things to be approached mechanically, rather than physiologically. The lens’s circulatory system is very interesting, because of what it says about the nature of living substance. In the absence of blood vessels, it provides its own flow of nutrients. This flow is reminiscent of the flow of substances through the dentine channels of the teeth, through the axons of nerves (two-way transport in a very narrow channel), and, in some ways recalls the flow of fluids in plants, called “guttation” (drop formation), which is disturbing to botanists, because it is contrary to the textbook descriptions of proper physiology.

眼睛的晶状体通常被视为一种非常特殊的东西,几乎不被认为是我们生命的一部分,就像牙科倾向于把牙齿视为惰性的东西,需要从机械上而不是生理上加以处理一样。晶状体的循环系统非常有趣,因为它反映了生命物质的本质。在没有血管的情况下,它自己提供营养。这种流动让人联想到物质通过牙齿的牙质通道,通过神经轴突(在一个非常狭窄的通道中双向运输)的流动,在某种程度上,让人想起植物中液体的流动,称为“滴状”(滴状形成),这让植物学家感到不安,因为这与教科书上的生理学描述相反。

The flow of material through lens cells, dentine canals, and nerve axons should allow us to gain a perspective in which these observable processes become a model for other biological situations in which “transport” occurs: Kidney, intestine, or the skin of frogs, for example, in which water, ions, and other solutes are moved in considerable quantities.

物质通过晶状体细胞、牙本质管和神经轴突的流动应该让我们获得一个视角,在这种视角下,这些可观察到的过程将成为“运输”发生的其他生物情况的模型:例如青蛙的肾、肠或皮肤,水、离子和其他溶质在其中大量流动。

When cells metabolize, they create gradients. In the cell, electrical, chemical, osmotic, and thermal gradients, for example, are constantly being produced or maintained. The whole substance of the cell is involved in its life processes. Because of prejudices introduced 200 years ago, the life of the cell has been relegated to its “membrane” (where hypothetical “membrane pumps” reside) and its nucleus. When the term “cell” (hollow space) came into use instead of “corpuscle’ (little body), a mind-set came into existence that discounted the importance of most of the living material, and claimed that it was a mere “random solution.” Random solutions don’t do much. The wonderful “membrane,” under the direction of the nucleus (and its set of instructions), took care of everything.

当细胞代谢时,它们会产生梯度。例如,在细胞中,电梯度、化学梯度、渗透梯度和热梯度不断产生或维持。细胞的全部物质都参与它的生命过程。由于200年前引入的偏见,细胞的生命已被降级为它的“膜”(假设的“膜泵”居住的地方)和它的核。当术语“细胞”(中空的空间)取代“小体”(小体)开始使用时,一种思维模式就产生了,这种思维模式忽视了大多数生命物质的重要性,并声称它只是一个“随机的解决方案”。随机解决方案没有多大作用。奇妙的“膜”在细胞核(及其指令)的指导下,照料着一切。

Whenever assimilation or excretion took place, it was explained by inventing a property possessed by the cell “membranes.” Therefore, we have physiology textbooks that have an unfounded explanation for everything. Before Copernicus, planetary movements were described as arbitrary “epicycles.” They didn't make sense, but people studied them and felt that they were important. “Membrane physiology” is the modern equivalent of the Ptolemaic epicycles.

每当发生同化或排泄时,就会发明一种由细胞膜所拥有的特性来解释。因此,我们的生理学教科书对所有事情都有毫无根据的解释。在哥白尼之前,行星运动被描述为任意的“本轮”。它们没有意义,但人们研究它们,觉得它们很重要。“膜生理学”是托勒密的本轮学说的现代版。

We know that glucose can be metabolized into pyruvic acid, which, in the presence of oxygen, can be metabolized into carbon dioxide. Without oxygen, pyruvic acid can be converted into lactic acid. The production of lactic acid tends to increase the pH inside the cell, and its excretion can lower the pH outside the cell.

我们知道葡萄糖可以代谢成丙酮酸,丙酮酸在氧气存在的情况下,可以代谢成二氧化碳。没有氧气,丙酮酸可以转化为乳酸。乳酸的产生往往会增加细胞内的pH值,而乳酸的排泄则会降低细胞外的pH值。

The decrease of carbon dioxide that generally accompanies increased lactic acid, corresponds to increased intracellular pH. Carbon dioxide binds to many types of protein, for example by forming carbamino groups, changing the protein conformation, as well as its electrical properties, such as its isoelectric point. With increased pH, cell proteins become more strongly ionized, tending to separate, allowing water to enter the spaces, in the same way a gel swells in an alkaline solution.

通常伴随着乳酸增加的二氧化碳减少,对应于细胞内ph值的增加。二氧化碳与许多类型的蛋白质结合,例如通过形成氨基,改变蛋白质的构象,以及它的电学性质,如等电点。随着pH值的增加,细胞蛋白质变得更强的电离,倾向于分离,让水进入空间,就像凝胶在碱性溶液中膨胀一样。

The Bohr-Haldane effect describes the fact that hemoglobin releases oxygen in the presence of carbon dioxide, and releases carbon dioxide in the presence of oxygen. When oxygen is too abundant, it makes breathing more difficult, and one of its effects is to cause carbon dioxide to be lost rapidly. At high altitude, more carbon dioxide is retained, and this makes cellular respiration more efficient.

玻尔-霍尔丹效应描述的事实是,血红蛋白在有二氧化碳的情况下释放氧气,并且在有氧气的情况下释放二氧化碳。当氧气过多时,呼吸就会变得更加困难,其后果之一就是导致二氧化碳迅速流失。在高海拔地区,更多的二氧化碳被保留下来,这使得细胞呼吸更加有效。

The importance of carbon dioxide to cell control process, and to the structure of the cell and the structure of proteins in general suggested that degenerative diseases would be less common at high altitude. Wounds and broken bones heal faster at high altitude, but the available statistics are especially impressive in two of the major degenerative conditions, cancer and cataracts.

二氧化碳对细胞控制过程、细胞结构和蛋白质结构的重要性表明,退化性疾病在高海拔地区不太常见。在高海拔地区,伤口和骨折愈合得更快,但现有的统计数据在两种主要的退行性疾病——癌症和白内障方面尤其令人印象深刻。

The two biggest studies of altitude and cataracts (involving 12,217 patients in one study, and 30,565 lifelong residents in a national survey in Nepal) showed a negative correlation between altitude and the incidence of cataract. At high altitude, cataracts appeared at a later age. In Nepal, an increase of a few thousand feet in elevation decreased the incidence of cataracts by 2.7 times. At the same time, it was found that exposure to sunlight increased the incidence of cataracts, and since the intensity of ultraviolet radiation is increased with altitude, this makes the decreased incidence of cataracts even more important.

两项关于海拔和白内障的最大研究(其中一项研究涉及12217名患者,在尼泊尔进行的一项全国调查涉及30565名终身居民)显示,海拔与白内障发病率之间存在负相关关系。在高海拔地区,白内障出现的年龄较晚。在尼泊尔,海拔升高几千英尺,白内障的发病率就降低了2.7倍。与此同时,研究发现,暴露在阳光下会增加白内障的发病率,而且由于紫外线辐射强度随海拔高度的增加而增加,这就使得降低白内障发病率变得更加重要。

All of the typical causes of cataracts, aging, poisons, and radiation, decrease the formation of carbon dioxide, and tend to increase the formation of lactic acid. Lactic acid excess is typically found in eyes with cataracts.

引起白内障、衰老、中毒和辐射的所有典型原因都减少了二氧化碳的形成,并倾向于增加乳酸的形成。患有白内障的眼睛通常会出现乳酸过量。

The electrical charge on the structural proteins will tend to increase in the presence of lactic acid or the deficiency of carbon dioxide, and the increase of charge will tend to increase the absorption of water.

在乳酸存在或二氧化碳缺乏的情况下,结构蛋白上的电荷倾向于增加,电荷的增加倾向于增加对水的吸收。

The lens can survive for a considerable length of time in vitro (since it has its own circulatory system), so it has been possible to demonstrate that changes in the composition of the fluid can cause opacities to form, or to disappear.

晶状体在体外可以存活相当长的时间(因为它有自己的循环系统),因此有可能证明,液体成分的变化会导致混浊的形成或消失。

Oxidants, including hydrogen peroxide which occurs naturally in the aqueous humor, can cause opacities to form quickly, but they will also disappear quickly in a solution that restores metabolic energy. The lens regulates itself powerfully; for example, it will swell when put into a hypotonic solution, but will quickly adapt, returning to approximately its normal size.

氧化剂,包括在水溶液中自然存在的过氧化氢,可以导致快速形成不透明,但它们也会在恢复新陈代谢能量的溶液中迅速消失。镜头自我调节能力很强;例如,当它被放入低渗溶液时,它会膨胀,但会很快适应,恢复到大约正常的大小。

Several years ago, I saw what appeared to be oxidant-induced cataracts. Two women had a very sudden onset of cataracts, and I asked about their diet and supplements; it turned out that one of them had begun taking 500 mg of zinc daily a few months earlier, and the other had begun taking 600 mg of zinc and 250 mg of iron, on her doctor’s recommendation, just a couple of months before the cataracts appeared.

几年前,我看到了氧化剂引起的白内障。两名妇女突然患上白内障,我询问她们的饮食和补品;结果发现,其中一名患者在几个月前就开始每天服用500毫克的锌,而另一名患者在出现白内障的几个月前,根据医生的建议,开始服用600毫克的锌和250毫克的铁。

For some reason, there have been many nutritional supplements sold as cataract remedies in the form of eye drops. I suppose a trace of the material could diffuse through the cornea into the aqueous humor, where it might make a difference in the lens’s nutrient supply, but it seems more reasonable to treat the body as a whole, nourishing every part in a balanced way.

由于某些原因,有许多营养补充剂以眼药水的形式作为白内障治疗手段出售。我想,这种物质的痕迹可能会通过角膜扩散到房水中,在那里它可能会对晶状体的营养供应产生影响,但似乎更合理的做法是把身体作为一个整体来对待,以平衡的方式滋养每个部分。

Besides living at a high elevation or breathing extra carbon dioxide, the most certain way to increase the amount of carbon dioxide in the eye, and to prevent an excess of lactic acid, is to make sure that your thyroid function is adequate.

除了生活在高海拔地区或呼吸额外的二氧化碳,增加眼睛中二氧化碳含量和防止乳酸过量的最确定的方法是确保你的甲状腺功能充足。

One man who took thyroid, USP, and vitamin E told me that his cataracts had regressed, but I haven’t known other people who tried this.

一个服用甲状腺、USP和维生素E的人告诉我,他的白内障已经消退了,但我不知道还有谁尝试过这种方法。

If a person already has distinct cataracts, it might be worthwhile to experiment with a relatively high degree of hypercapnia, for example, breathing a 5% mixture of CO2 in air.

如果一个人已经患有明显的白内障,那么做一个相对高碳酸血症的实验可能是有价值的,例如,呼吸空气中5%的二氧化碳混合物。

Carbon dioxide, at higher levels than are normal at sea level, has a profound effect on free radicals, reducing the free radical activity in the blood to approximately zero, before reaching the level that produces acidosis.

二氧化碳浓度高于海平面的正常水平,会对自由基产生深远的影响,在达到产生酸中毒的水平之前,会将血液中的自由基活性降低到接近零的水平。

There are several situations in which carbon dioxide affects the hydration, water content, of biological materials, that I think give an insight into its effects on the lens. Hydrophilic glycoproteins are involved in each case. These are proteins with attached chains of sugar molecules that make them associate with a large amount of water. In the cornea, increased carbon dioxide strongly protects against swelling. The bulk of the cornea is a connective tissue that is relatively simple and passive compared to the compact cellular structure of the lens, and it is conventional to describe the thin layers of cells on the inside and outside of the cornea as being responsible for the water content of the underlying substance. However, even when the epithelial cells are removed, it has been demonstrated that carbon dioxide is able to prevent corneal swelling. (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.)

在一些情况下,二氧化碳会影响生物材料的水合作用和含水量,我认为这可以让我们了解二氧化碳对镜片的影响。每一种情况都涉及亲水性糖蛋白。这些蛋白质与糖分子链相连,使它们与大量的水联系在一起。在角膜中,增加的二氧化碳可以有效地防止肿胀。角膜的大部分是结缔组织,相对简单的和被动的细胞结构紧凑镜头相比,是传统的薄层细胞内外的角膜是负责底层物质的含水量。然而,即使上皮细胞被移除,二氧化碳也能防止角膜肿胀。(M.V. Riley等人,“碳酸氢盐和二氧化碳在跨内皮流体运动和角膜厚度控制中的作用”,Invest。角膜切削。中国科学(d辑:地球科学),37(4):527 - 534,1995。

Bronchial mucous secretions are an even simpler system, so it is very interesting that carbon dioxide is recognized as the most powerful regulator of their behavior. (This has important implications for “cystic fibrosis,” or mucoviscidosis.) Goodman and Gilman (page 1068, Pharmacological Basis of Therapeutics,2nd Edition, Macmillan Co., 1956), say

“Among inhalants, steam and carbon dioxide have been found to be excellent expectorants. Relative humidity above 85 per cent liquefies sputum, decreases its viscosity….” “Carbon dioxide is the most effective agent of all. It not only lowers the viscosity of tenacious sputum, thereby facilitating expectoration, but it decreases the volume of sputum by promoting its active resorption by bronchial mucosa.” “A five to ten per cent concentration of carbon dioxide is adequate and well tolerated if administered at intervals.” “Oxygen has been shown to be an antiexpectorant and has effects opposite to those of carbon”

支气管粘膜分泌物是一个更简单的系统,所以很有趣的是,二氧化碳被认为是它们行为的最强大的调节器。(这对“囊性纤维化”或粘液粘性病有重要意义。)古德曼和吉尔曼(1068页,治疗学药理学基础,第二版,麦克米伦公司,1956年),说在吸入剂中,蒸汽和二氧化碳被发现是极好的祛痰剂。85%以上的相对湿度使痰液液化,降低其黏度….”“二氧化碳是所有药剂中最有效的。它不仅能降低顽固痰液的黏度,从而促进咳痰,还能通过促进支气管粘膜的积极吸收来减少痰液的体积。”“如果每隔一段时间给药,5%到10%的二氧化碳浓度就足够了,而且耐受性很好。”氧已被证明是一种祛痰剂,其作用与碳相反。

Oxygen tends to displace carbon dioxide from tissue, and is a source of free radicals.

氧会取代组织中的二氧化碳,是自由基的来源。

One of the best-known free radical scavenging substances that has been widely used as a drug is iodide. It has been used to treat asthma, parasites, syphilis, cancer, Graves’ disease, periodontal disease, and arteriosclerosis. Diseases that produce tissue overgrowth associated with inflammation–granulomas–have been treated with iodides, and although the iodide doesn’t necessarily kill the germ, it does help to break down and remove the granuloma. Leprosy and syphilis were among the diseases involving granulomas* that were treated in this way. In the case of tuberculosis, it has been suggested that iodides combine with unsaturated fatty acids which inhibit proteolytic enzymes, and thus allow for the removal of the abnormal tissue.

碘化物是目前广泛使用的清除自由基的药物之一。它已被用于治疗哮喘、寄生虫、梅毒、癌症、格雷夫斯病、牙周病和动脉硬化。与炎症相关的组织过度生长的疾病——肉芽肿——已经被碘化剂治疗过了,尽管碘化剂不一定会杀死病菌,但它确实有助于分解和清除肉芽肿。麻风病和梅毒是通过这种方式治疗的肉芽肿疾病*。在肺结核病例中,有人认为碘与抑制蛋白水解酶的不饱和脂肪酸结合,从而使异常组织得以清除。

In experimental animals, iodide clearly delays the appearance of cataracts. (Buchberger, et al., 199l.)

在实验动物中,碘明显延缓白内障的出现。(Buchberger等,199l.)

Inflammation, edema, and free radical production are closely linked, and are produced by most things that interfere with energy production.

炎症、水肿和自由基的产生是密切相关的,并且是由大多数干扰能量产生的东西产生的。

Endotoxin, produced by bacteria, mainly in the intestine, disrupts energy production, and promotes maladaptive inflammation. The wide spectrum of benefit that iodide has, especially in diseases with an inflammatory component, suggests first that it protects tissue by blocking free radical damage, but it also suggests the possibility that it might specifically protect against endotoxin.

内毒素,由细菌产生,主要在肠道,扰乱能量生产,并促进不适应的炎症。碘具有广泛的益处,特别是在具有炎症成分的疾病中,这首先表明它通过阻止自由基损伤来保护组织,但它也表明它可能专门保护内毒素。

There are subtler differences in transparence that probably have a variety of causes, but differences in water content or hydration might be involved in the lower transparency that has been seen in women's lenses. Estrogen, which tends to produce edema and hypotonic body fluids, also increases prolactin production. Prolactin is involved in water and electrolyte regulation, and it has been found to accelerate the development of experimental cataracts. (M. C. Ng, et al, 1987.) These hormones are associated with the calcification of soft tissues, and cataracts contain very high levels of calcium. (Avarachan and Rawal, 1987; Hightower and Reddy, 1982.)

透明度的细微差异可能有多种原因,但含水量或水合作用的差异可能与女性晶状体的低透明度有关。雌激素,往往产生水肿和低渗体液,也增加催乳素的生产。催乳素参与水和电解质的调节,它已被发现加速实验性白内障的发展。(M. C. Ng等,1987.)这些激素与软组织的钙化有关,白内障的钙含量非常高。(Avarachan和Rawal, 1987;Hightower和Reddy, 1982年)。

Estrogen is strongly associated with free radical processes, calcium mobilization, and acetylcholine release, all of which are involved in the process of excitoxicity. Alvarez, et al., (1996) have shown a possible involvement of acetylcholine in calcium mobilization in the lens.

雌激素与自由基过程、钙动员和乙酰胆碱释放密切相关,所有这些都涉及兴奋性过程。Alvarez等人(1996)已经证明乙酰胆碱可能参与晶状体内钙的动员。

Serotonin is another regulatory substance strongly associated with prolactin and estrogen, and it also can be involved in disrupting the metabolism of the lens. This is one of the potential dangers in using supplemental tryptophan. (Candia, et al., 1980.)

血清素是另一种与催乳素和雌激素密切相关的调节物质,它也可以参与破坏晶状体的新陈代谢。这是使用补充色氨酸的潜在危险之一。(Candia等,1980.)

Old age commonly involves some changes in the color of tissues–loss of pigment from hair and skin, with appearance of new pigment (age pigment, lipofuscin), which may appear as “liver spots.” But there is also a tendency of the toenails, fingernails, teeth, and lenses to turn yellow or brown. Some of this dark material seems to be age pigment, derived from unsaturated fatty acids, but other components have been identified, for example, tryptophan from damaged proteins. 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.

衰老通常涉及组织颜色的一些变化——毛发和皮肤色素的丢失,出现新的色素(年龄色素、脂褐素),这些色素可能出现“肝斑”。但脚趾甲、指甲、牙齿和镜片也有变黄或棕色的趋势。其中一些黑色物质似乎是来自不饱和脂肪酸的老年性色素,但也发现了其他成分,例如,来自受损蛋白质的色氨酸。美拉德反应(类似于发生在面包皮上的褐变)经常被提到与老化有关,涉及蛋白质氨基与糖的结合。但晶状体的褐变往往与一般年龄相关的干燥,它不是不规则分布的,它不会严重损害视力。

When 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.

当我第一次听说与年龄有关的镜片褐变时,我认为颜色的体验会受到影响,所以我设计了一个测试,在这个测试中,蓝色和黄色的相对黑暗程度可以与灰色的渐变条带相比较来判断。

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.

在年龄从10岁到80岁的人给出完全相同的匹配后,我意识到神经系统可能纠正了棕色镜片的“黄色过滤”效果。

The browning of tissues will be the subject of another newsletter.

组织的褐变问题将成为另一份时事通讯的主题。

Among the interesting causes of cataracts: Tamoxifen and hypotonic fluids, sodium deficiency; toxicity of tryptophan; oxidants (metals, hydrogen peroxide, PUFA); diabetes, photosensitizers and sunlight; 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.

引起白内障的原因有:他莫昔芬和低渗液体、钠缺乏;色氨酸的毒性;氧化剂(金属、过氧化氢、多不饱和脂肪酸);糖尿病、光敏剂和阳光;钙过量,镁缺乏。过多的皮质醇。辐射。花生四烯酸和亚油酸在其他情况下被发现会阻碍细胞对其水分含量的调节。甲状腺机能减退会增加血清素、雌激素、催乳素、钙的活性,以及组织保持水分的倾向,并降低ATP水平。

Among the factors that probably have a role in preventing cataracts: 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.

预防白内障的因素有:甲状腺、孕酮、孕烯酮、维生素E、碘化物、丙酮酸。增加二氧化碳会降低细胞的pH值,并倾向于抵抗肿胀。棕榈酸(一种可以由人体组织合成的饱和脂肪)通常会被晶状体氧化。从实验上看,钙阻滞剂可以预防白内障,这表明镁和甲状腺(它们也能从细胞中排除钙)也有同样的效果。

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.

甲状腺激素对于维持足够的二氧化碳产量,减少乳酸、皮质醇和催乳素,调节钙和镁,避免体液低渗,以及提高棕榈酸和亚油酸的比例都是必不可少的。

REFERENCES

引用

“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. 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.”

5 -羟色胺类似物对离体蟾蜍晶体中离子转运和atp酶活性的抑制作用Lanzetta PA;阿尔瓦雷斯LJ;王志强,王志强,王志强,等。中国生物化学学报(英文版)。“色胺、5-甲基色胺和5-甲氧基色胺有双重作用:后浴液1 mM降低晶状体后面电位差,导致透晶状体电位差增加和短路电流;在前液中1毫米(与晶状体上皮接触)产生的前脸电位差迅速和明显的减少。这导致了90-100%的跨晶状体短路电流下降。然后测试血清素和色胺对晶状体上皮atp酶的影响。这两种胺都在5 mM时用色胺抑制酶,完全抑制了所有atp酶活性。由于色氨酸从房水运输到晶状体,并可能通过晶状体酶转化为血清素和色胺,这些发现可能对白内障发生具有生理学意义。”

“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.“

“Ca2+对兔翻译短路电流的影响:Ca2+可抑制K+电导的证据”,Alvarez LJ;‧办公自动化;Zamudio AC, Curr Eye Res, 1996年12月15日,1198-207。目的:研究中等钙离子水平对兔晶状体电特性的影响。总之,这些结果表明,晶状体Ca2(+)动员剂(如乙酰胆碱)可以通过Ca2+对K+通道的直接作用触发上皮细胞K+电导的抑制。”

“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.“

D600增加与晶体赤道钾电流相关的电阻,”Walsh SP;这种效应与奎宁和无钙介质产生的效应相似,可归因于pCMPS产生的钙依赖电导的增加的预防。

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 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. These effects of hydrogen peroxide are similar to those of p-chloromercuriphenylsulfonate(pCMPS), a nearly impermeant sulfhydryl binding agent, 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.

过氧化氢氧化和钙通道阻断剂对蛙晶状体赤道钾电流的影响”。林志强,1994,4(3):1 - 7。“过氧化氢,浓度在10-1000微米,在与镜头的赤道钾电流相关的电流电压关系中产生两个主要变化。首先,静息电位和逆转电位比过氧化氢处理前更负,其次,与赤道电流相关的膜阻力降低。静息电位和反转电位的转移与ouabain产生的方向相反。根据能斯特方程,反转电位的变化表明透镜中钾的浓度增加了。86Rb的摄取和流出增加。这些观察表明,过氧化氢刺激钠,钾泵。100微米的奎宁(一种钙依赖性钾通道阻滞剂)可抑制膜电阻的降低,在无钙介质中不会降低。这表明,电阻的下降可能是继发于晶状体钙的增加。过氧化氢的这些作用类似于对氯汞苯磺酸盐(pCMPS)的作用,pCMPS是一种几乎没有意义的巯基结合剂,这表明过氧化氢可以通过作用于透镜膜外表面的巯基而增加钙的内流。据报道,钙通道阻滞剂维拉帕米可以预防白内障的形成。

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.

催乳素对半乳糖白内障发生的影响徐司法院;Merola瞧;国家自然科学基金项目:国家自然科学基金项目。“众所周知,催乳素会影响水和电解质平衡。由于晶状体水合作用增加已被证明是大多数(如果不是所有类型的)白内障的普遍现象,我们一直有兴趣研究催乳素在糖性白内障诱导和进展中的可能作用。在这项研究中,我们使用了形态学和生化方法。催乳素输送方法包括在斯普拉格-道利雌性大鼠腹腔内植入一个或多个颗粒。植入所需数量的催乳素或对照组(非催乳素)颗粒后,动物喂食半乳糖和实验室饲料,或实验室饲料。全晶状体大体形态学观察、晶状体裂隙灯检查和晶状体切片光镜分析显示,半乳糖喂养的催乳素组比非催乳素组半乳糖相关改变进展更快,完全混浊(成熟白内障发展)更早。服用催乳素的大鼠晶状体中的半乳糖和甘露糖醇水平高于未服用催乳素的大鼠晶状体。催乳素组与非催乳素组晶状体Na+-K+ atp酶活性无显著差异。我们的结果表明,催乳素加速半乳糖诱导的大鼠白内障发生。

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 coincide with those that catalyze oxidative damage to lipids. 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 would uncouple the Na+/K(+)-ATPases that regulate the water and ionic content of the bounded tissue. Once regulatory control of the osmotic pressure is lost, the phase state of the cell's soluble proteins would change, leading to refractive changes or, in extreme cases, precipitation. 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.

由于晶状体上皮膜氧化损伤而导致的中毒性白内障的假设机制,”Bender CJ Med Hypotheses, 1994 Nov, 43:5, 307-11,可以由许多外部因子与那些催化脂质氧化损伤的因子共同诱导晶状体混浊。脂质过氧化的后果之一是受影响的膜对质子更具渗透性。晶状体致密上皮内的质子泄漏将使Na+/K(+)- atp酶解耦,该酶调节结界组织中的水和离子含量。一旦失去了对渗透压的调节控制,细胞可溶性蛋白质的相态就会改变,导致折射变化,或者在极端情况下,导致沉淀。同样的情况不会发生在角膜中,因为基质是细胞外聚合物的混合物,而不是可溶性聚合物的溶液。角膜中的聚合物相变需要二价阳离子通过上皮膜,而这只能通过离子载体的作用发生。

Tsubota K; Laing RA; Kenyon KR Invest Ophthalmol Vis Sci, 1987 May, 28:5, 785-9, Abnormalities in glucose metabolism are thought to be among the main causes of cataract formation. 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 (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 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.”

Tsubota K;莱恩风湿性关节炎;葡萄糖代谢异常被认为是白内障形成的主要原因之一。作者对晶状体进行了无创生化测量,提供了有关晶状体上皮内葡萄糖代谢的信息。用氧化还原荧光法无创测量兔晶状体内还原吡啶核苷酸(PN)和氧化黄酮类蛋白(Fp)的自荧光随深度的变化。在晶状体上皮处检测到440nm处(360 nm处激发)和540nm处(460 nm处激发)的自荧光峰。8 mM戊巴比妥钠是一种已知的线粒体呼吸抑制剂,当应用于晶状体时,440 nm处的自荧光峰增加,540 nm处的自荧光峰减少。440nm的自荧光被认为来自于还原的吡啶核苷酸,而540 nm的自荧光来自于氧化的黄素蛋白。用戊巴比妥阻断晶状体呼吸可使PN/Fp在应用戊巴比妥后3.5小时内增加3倍。”

[Use of pyrimidine bases and ATP for conservative treatment of early cataracts] Larionov LN Oftalmol Zh, 1977, 32:3, 221-2

[嘧啶碱基和ATP在早期白内障保守治疗中的应用

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 high levels of L-lactate and high ratios of L-lactate in the lens/L-lactate in the aqueous. 2. Immature cataractous lenses with anterior capsular/subcapsular opacity; intermediate levels of RTP, intermediate values for the sums of RTP, RDP, and AMP, high L-lactate levels, and intermediate values of the ratios of L-lactate in the lens/L-lactate in the aqueous.

在人类老年性白内障晶状体中某些核糖核酸、l -乳酸和丙酮酸的浓度,特别是与前囊/下囊混浊有关,”Laursen AB Acta Ophthalmol (Copenh), 1976年12月,54:6,677-92测定了白内障手术摘除的老年白内障晶状体中l -乳酸和丙酮酸的含量。在15例老年白内障晶状体中,丙酮酸浓度可以忽略不计(中位数= 56 mumol/kg晶状体湿重)。根据老年白内障晶状体(N = 80)的生物显微镜外观与相关代谢物的浓度和比例之间的相关性,我们发现以下分类是合理的:1。未成熟白内障晶状体无前囊/囊下混浊:晶状体中有高水平的三磷酸核糖核苷(RTP)、高水平的三磷酸核糖核苷(RDP)、二磷酸核糖核苷(RDP)和腺苷5'-单磷酸腺苷(AMP),晶状体中有高水平的l -乳酸和高比例的l -乳酸/水溶液中l -乳酸。2. 未成熟白内障晶状体,前囊或下囊混浊;中间水平的RTP,中间值的RTP, RDP和AMP的总和,高的l -乳酸水平,中间值的l -乳酸在晶状体中的比率/水中的l -乳酸。

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. The same was found accumulated in the blood and lenses of affected children. 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 activity of beta glucuronidase in lymphocytes and urine, 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 beta glucuronidase activity might have caused extensive fragmentation of GAG 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.

Sulochana KN;Ramakrishnan年代;Vasanthi某人;Madhavan HN;Arunagiri K;陈建平,“先天性或婴儿白内障伴木糖代谢紊乱的临床报告”,中华眼科杂志,1997,4:421 - 423。“在印度马德拉斯市Sankara Nethralaya治疗的220名患有先天性或婴儿白内障的12岁以下男女儿童中,有145人在尿液中排泄了GAG碎片(硫酸肝素和硫酸软骨素)。对照组50例患儿无此类排泄。在受影响儿童的血液和晶状体中也发现了同样的物质。此外,尿液和血液中有少量木糖,晶状体中有木糖醇。与正常人相比,淋巴细胞和尿液中-葡醛酸酶活性显著升高。以上结果表明蛋白多糖代谢紊乱。由于尿液中含有大部分GAG碎片和非常少的木糖,本尼迪克特的试剂没有减少。这就排除了半乳糖血症。结论:葡萄糖醛酸酶活性的增加可能引起广泛的GAG碎裂,从而在血液和晶状体中积累并在尿液中排泄。少量木糖可能来自GAG和蛋白多糖的核心蛋白之间的木糖连接。由于它们的聚阴离子性质,晶状体中的GAG碎片可能会吸收钠和水,从而增加晶状体的水合作用。过度的水合作用和木糖产生的木糖醇的渗透作用可能导致白内障。虽然先天性酸性粘多糖病有角膜混浊的报道,但由于蛋白多糖(酸性粘多糖-木糖-蛋白复合物)代谢紊乱的先天性或婴儿白内障在儿童中首次被报道。

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, several fold increment of calcium; considerable loss of magnesium levels, a dose-response reduction of total-ATPase activity and significant hydration are the important features 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 an abnormal accumulation of calcium ions 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.

亚硒酸盐诱导白内障晶状体中电解质状态、渗透平衡和atp酶活性的研究印度眼科杂志,1987,35:5-6,210-3。“亚硒酸盐白内障包含了在人类老年性白内障中观察到的许多形态特征。钠逐渐升高,钾明显流失,钙成倍增加;在亚硒酸盐渐进治疗过程中,晶状体中观察到的重要特征是镁水平的相当大的损失,总atp酶活性的剂量反应性降低和显著的水合作用。钠钾失衡是白内障发生过程中的一种副反应,可能是由于钙离子的异常积累和转运酶的失活所致。钙活化蛋白酶可能是诱发亚硒酸盐白内障晶状体蛋白水解和不溶的促进因子。亚硒酸盐对含atp酶酶的SH的影响可能是能量代谢障碍、电解质紊乱和渗透失衡的原因,进而加速皮质对晶状体混浊的累及。

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. An ATP concentration of 3 mM was found to inhibit lactate production.

培养中的人类白内障的葡萄糖代谢,”Wolfe JK;Chylack LT Jr Exp眼Res 43:2, 243-9, 1986。“使用统一标记的[14C]葡萄糖研究了人类老年性白内障的代谢。囊内摘除的晶状体在葡萄糖浓度为5.5 mM的TC-199培养基中培养。结果显示,乳酸生成占代谢葡萄糖的97%。在这些标准的培养条件下,α -甘油磷酸、葡萄糖-6-磷酸和山梨醇的积累可以忽略不计。根据CCRG分类,在一系列白内障严重程度上,乳酸产生率是相对一致的。测量了介质中几种微扰的影响。发现ATP浓度为3mm时可抑制乳酸生成。

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. “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.”

重碳酸盐和二氧化碳在跨内皮流体运动和角膜厚度控制中的作用,投资。角膜切削。中国科学(d辑:地球科学),37(1),413 - 418,1995。在两种表面用HCO-/CO2肿胀的深层上皮化角膜的平衡厚度比用HPO4-肿胀的角膜的平衡厚度少35微米。只有在含HCO3-浓度超过20毫米的培养基中,才能在体外维持正常角膜厚度。

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. The unaltered Na-K-ATPasecontent in the epithelium suggests that the hydration of the lens after X-irradiation is primarily caused by changes in the passive permeability properties of the cell membranes and not by a decreased capacity of the activity cation pump.

x射线照射对大鼠晶状体上皮钠钾活化腺苷三磷酸酶(na - k - atp酶)活性的影响。《中华眼科杂志》,1978年6月,56:3,431-8。“在间隔3至90天的x光照射后,研究了大鼠晶状体上皮na - k - atp酶的活性。该酶通过光镜组织化学证明,并通过荧光法进行生物化学测定。在白内障的发展过程中,晶状体上皮na - k - atp酶含量未见组织化学或生化变化。在全包体制剂中,酶活性定位于细胞膜。然而,辐射一个月后,少数外周细胞在整个细胞上有沉淀。上皮细胞中na - k - atp酶的含量未发生改变,提示x射线照射后晶状体的水化主要是由于细胞膜的被动通透性的改变,而不是由于活性阳离子泵容量的降低。

McNamara NA; Polse KA; Bonanno JA “Stromal acidosis modulates corneal swelling.” 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. 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. Before and after 2.5 hours of gas exposure, central corneal thickness (CCT) was measured. RESULTS. Eyes exposed to the lower pH environment (eg, N2 + CO2) developed less change in CCT 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 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 exerts its effect only under non-steady-state conditions (ie, corneal swelling and deswelling). This suggests that acidosis may produce changes in the rate of lactate metabolism or alter endothelial hydraulic conductivity.”

麦克纳马拉NA;脉冲KA;Bonanno JA“基质酸中毒调节角膜肿胀。”投资眼科科学,1994年3月,35:3,846-50”研究表明,基质酸中毒降低了诱导水肿后角膜厚度恢复的速度,这为角膜pH值影响角膜水化控制提供了第一个人体内证据。这一发现提出了pH值可能对诱导角膜肿胀有影响的问题。为了探讨这个问题,在基质pH控制下测量角膜对缺氧的肿胀反应。方法。10名受试者通过戴紧的护目镜将氮气和二氧化碳的混合物通过眼睛,引起角膜水肿和间质酸中毒。每个受试者一只眼接受100% N2,而对侧眼接受95% N2和5% CO2的混合物。暴露在95%的N2 + 5%的CO2中,pH值平均降低到7.16,而单独暴露在100%的N2中pH值为7.34。在气体暴露2.5小时前后,测量角膜中央厚度(CCT)。结果。暴露于较低pH值环境(如N2 + CO2)的眼睛与单独接受N2的眼睛相比,CCT的变化较小。暴露于95% N2 + 5% CO2气体混合物的眼睛CCT的总体增加为29.9±5.3微米,而100% N2的眼睛CCT增加为37.1±4.8微米(P < 0.0001)。结论。降低基质pH值可以降低角膜对缺氧的肿胀反应。由于尚未发现仅角膜pH值的变化就会改变稳态的CCT,因此建议pH值仅在非稳态条件下(即角膜肿胀和肿胀)才会产生影响。这表明酸中毒可能会改变乳酸代谢速率或改变内皮细胞的水力传导能力。”

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. Iodide treatment induced a delay of cataract formation….” “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 to the known antioxidant and .OH-scavenging effect of iodide and to the oxidative changes in the lens occurring during progression of cataract development.”

Buchberger W;温克勒R;莫泽M;李文杰,“碘对小鼠白内障发生的影响”,中华眼科杂志,1998,21(3):421 - 427。通过定期生物显微镜检查(从5周龄开始)和对晶状体中水溶性SH组的最终评估,研究了两组Emory小鼠的白内障发展情况。实验组在整个研究过程中饮用256微克/公斤体重的碘化物。未处理的对照组饮用自来水。碘治疗延迟白内障形成….““在第47周时,两组患者的白内障程度也存在显著差异。水溶性SH基团含量无显著差异。研究结果与碘化物已知的抗氧化作用和。oh清除作用以及白内障发展过程中晶状体中的氧化变化有关。”

”[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. “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.” “It was established that high-molecular weight fluorescent fractions corresponded to lipid components of lipofuscin-like pigments. NMR and mass spectrometry of low-molecular weight fractions suggested that they contained predominantly products of free radical oxidation of long chain polyunsaturated fatty acids (C22:6). ”

“遗传性白内障小鼠晶状体脂质中积累荧光产物的化学性质”,Shvedova AA;普拉东诺夫ES;Polianskii NB;Babizhaev马;Kagan VE bill Eksp Biol Med, 1987年3月,103:3,301-4。“从遗传性白内障小鼠晶状体中提取的脂质中,二烯缀合物(脂质氢过氧化物)的含量明显高于对照组。这同样适用于脂质过氧化最终产物的荧光特性。”“研究证实,高分子量荧光组分与类脂黄素色素的脂质组分相对应。低分子量组分的核磁共振和质谱表明,它们主要含有长链多不饱和脂肪酸自由基氧化的产物(C22:6)。”

“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.

“通过暴露在阳光下,从透镜和其他来源的蛋白质中形成N'-甲酰kynurenine,”Pirie A Biochem J, 1971年11月,125:1,203-8。

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 (excitation maximum 302-330 nm, emission maximum 411 nm) with low polarity and a small molecular weight; the maturing of the cataract is 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 polymeric high-molecular-weight fluorescing lipid products with high polarity. It has been demonstrated that the appearance of lipid fluorophores in the crystalline lens is associated with the free radical oxidative modification of the phospholipids and fatty acids in cataract.

白内障患者晶状体的脂质荧光团“已经证实,白内障的发展伴随着晶体脂质部分中各种荧光团的形成。这些脂质荧光产物已根据极性和分子量进行了色谱分离。结果表明,白内障发展初期在近紫外光和紫外光区(激发最大302 ~ 330nm,发射最大411 nm)出现低极性、小分子量的脂质荧光团;白内障成熟的特征是蓝绿色区域(430-480 nm)脂质的长波荧光强度增加,并形成高极性的高分子脂质荧光产物。已有研究表明,晶状体中脂质荧光团的出现与白内障中磷脂和脂肪酸的自由基氧化修饰有关。

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 12,217 patients examined in the out-patient department (OPD), cataract surgery was performed on 2,163. The percentage of cataract patients in the OPD was less in the mountains (13.8%) than in the Tarai plains (19.8%). In the inhabitants of the mountains, the majority of whom belong to the Tibeto-Birman race, cataracts appeared at a significantly later age in both males and females compared to the people of the plains, who are mostly Indo-Aryan. Cataracts were discovered in both groups at a younger age in women than in men.

尼泊尔流动眼科医院的白内障发病率,“ Brandt F;沿着好;普拉丹YM;普拉萨德LN;Rai数控;Pokharel RP;尼泊尔的白内障发病率是根据14家流动眼科医院(称为“眼营”)收集的数据确定的。在12217例门诊患者中,2163例进行了白内障手术。山区白内障患者比例(13.8%)低于塔来平原地区(19.8%)。在山区的居民中,大多数是藏-伯曼族,无论男性还是女性,与平原地区的大多数印度-雅利安人相比,白内障出现的年龄都要晚得多。在这两组人中,女性患白内障的年龄比男性要小。

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 large national probability sample survey of 105 sites in the Himalayan kingdom of Nepal, December 1980 through April 1981. Cataract of senile or unknown etiology was diagnosed by ophthalmologists in 873 of 30,565 full-time life-long residents 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 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 (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.

白内障患病率、日照时间和喜马拉雅山的海拔高度之间的联系。”才华横溢的磅;份的数控;Pokhrel RP;Kolstad;Lepkowski JM;才华横溢的通用电气;鹰派WN;流行病学杂志118:2,250 -64 1983。“1980年12月至1981年4月,在喜马拉雅王国尼泊尔的105个地点进行了一次大型国家概率抽样调查,调查了白内障患病率、海拔和日照时间之间的关系。在调查地点30565名终身全职居民中,873名被眼科医生诊断为老年性白内障或病因不明的白内障。同时,利用标准山地高度计测量场地高度。每个地点经季节调整的每日平均日照时数是通过一种考虑了纬度和天际线上障碍物的方法计算的。在海拔185米及以下地区,年龄和性别标准化的白内障患病率比海拔1000米以上地区高2.7倍。白内障患病率与海拔高度呈负相关(r = -0.533, p < 0.0001)。白内障患病率与日照呈正相关(r = 0.563, p < 0.0001)。平均暴露在阳光下12小时的地区患白内障的几率是平均暴露在阳光下7小时的地区的3.8倍。附近的高山挡住了阳光照射到某些高海拔地区。

The untenability of the sunlight hypothesis of cataractogenesis,” Harding JJ Doc Ophthalmol 88:3-4, 345-9, 1994-95. “The excess prevalence of cataract in 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 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, but this was not found in brown cataract lenses. 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. Two studies showed that cataract was less common at higher altitude in the Himalayas, but unfortunately led to opposing conclusions. 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.

白内障发生的阳光假说的不成立,”哈丁眼科医生88:3-4,345-9,1994-95。“第三世界国家白内障的过度流行导致了本世纪初的一种假设,即阳光会导致白内障。这一假设忽略了饮食、文化、贫困和腹泻等其他疾病的流行,直到大约30年前,生物化学研究开始探索晶晶体蛋白的褐变,这是印度次大陆白内障的常见特征,才得到支持。起初这些研究是令人鼓舞的,因为暴露在阳光下会导致白内障晶状体的一些变化,但最终这个假设被否定了,因为实验室中的第一个变化是色氨酸的破坏,但这在棕色白内障晶状体中没有发现。棕色核白内障不能在实验室中用阳光或紫外线照射人工产生。接触实验动物会产生晶状体混浊,但在大多数实验中,所需剂量也会导致角膜炎、结膜炎、虹膜炎和炎症。角膜似乎比晶状体更敏感,这并不奇怪,因为它第一次有机会吸收有害的紫外线。对这一假设的生化排斥与流行病学研究的重新开始同时发生。这些研究大多只是纬度研究,只不过是六十年前的研究成果的重复。它们无助于找出原因。两项研究表明,白内障在喜马拉雅山的高海拔地区不太常见,但不幸的是得出了相反的结论。在普遍认识的基础上,紫外线暴露在更高的海拔更高,第一次海拔研究导致阳光假说的否定。

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.

维生素E的抗白内障作用:使用体外类固醇白内障模型的估计,” Ohta Y;冈田克也H;Majima Y;“本研究的目的是通过体外甲基强的松龙(MP)诱导的白内障模型来评估维生素E的抗白内障作用。6周龄雄性Wistar大鼠分离晶状体后,在TC-199培养基中加入MP (1.5 mg/ml),诱发相同程度的早期皮质性白内障。晶状体脂质过氧化氢(LPO)含量和Na+/K+比均轻微升高,还原性谷胱甘肽(GSH)含量和氧化应激敏感指标甘油醛-3-磷酸脱氢酶(GAP-DH)含量及Na+、K(+)- atp酶活性均轻微下降。在TC-199培养基中分别加入和不加入维生素E(250微克/毫升)孵育48小时后,维生素E处理的晶状体可防止白内障的进展,而维生素E未处理的晶状体则不能。未添加维生素E的晶状体维生素E含量降低,水分含量增加,LPO含量和Na+/K+比值进一步增加,GSH含量、GAP-DH和Na+,K(+)- atp酶活性进一步降低。相比之下,经维生素e处理的晶状体中除谷胱甘肽外,其他成分和酶的变化均减弱。从这些结果可以估计,维生素E可以通过保护晶状体免受氧化损伤和膜功能的丧失来预防MP治疗的大鼠晶状体体外白内障发生。

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 prevention of selenite cataract in vivo by intraperitoneal administration of pyruvate.

丙酮酸对大鼠晶状体氧化损伤的预防:体内可能的衰减,”Varma SD;拉马钱德兰年代;Devamanoharan PS;莫里斯SM;阿里啊,。“有研究评估丙酮酸对晶状体蛋白氧化及随后的变性和不溶的可能预防作用。本研究采用大鼠晶状体器官培养系统。水不溶蛋白(尿素溶)含量增加,如果晶状体培养在含双氧水的培养基。在培养基中加入丙酮酸防止了这种不溶作用。不溶作用主要与可溶性蛋白的晶体蛋白部分的损失有关。PAGE分析表明,不溶作用与- s - s -键的形成有关,丙酮酸可以防止- s - s -键的形成。由于丙酮酸是一种正常的组织代谢物,这一发现被认为对白内障的形成具有重要的病理生理学意义。通过腹腔注射丙酮酸对体内亚硒酸盐白内障的预防,这是明显的。

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. This change is reversible, and is interpreted as a protein-water phase separation that occurred during lens opacification.

拉曼光谱监测糖皮质激素诱导的鸡胚胎白内障,“ Mizuno A;Nishigori H;中国眼科杂志,30:1,132-7,1989。采用激光拉曼光谱监测糖皮质激素诱导的鸡胚白内障晶状体。鸡胚晶状体混浊是可逆的。拉曼光谱显示晶体混浊后,水的相对含量和蛋白质的二级结构均无明显变化。在透明透镜和不透明透镜之间,拉曼光谱中酪氨酸双峰的强度比发生了变化。这种变化是可逆的,被解释为在晶状体混浊过程中发生的蛋白质-水相分离。

[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) a gradual decrease of bound water content is noted, 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 explained by lens protein reconstructions during the cataract progression.

[对白内障发展过程中晶状体中水状态的核磁共振研究]”Babizhaev MA;Deev人工智能;Nikolaev GM, Biofizika 30:4, 671-4,1985。用核磁共振自旋回波法测定正常白内障晶状体和不同白内障进展阶段(初白内障、未成熟白内障、成熟超成熟白内障)晶状体中水质子自旋-自旋弛豫时间(T2)和-9℃下束缚“不冻”水的含量。到成熟性白内障阶段,束缚含水量增加,松弛时间(T2)减少近一半。然而,在随后的白内障评估阶段(几乎成熟、成熟白内障),束缚水含量逐渐下降,但只有成熟期的含水量与正常期有显著差异。在超成熟白内障阶段,发现有两个互不交换的水组分。所得数据可用白内障进展过程中的晶状体蛋白重建来解释。

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.”

Hightower KR;Reddy VN“钙++诱发白内障。”人工晶状体晶状体内钙含量升高引起白内障。实验程序成功地提高了总钙和结合钙的水平,通常没有显著变化的钠,钾,或水的含量。虽然过量的钙主要与水溶性蛋白质有关,并且是自由扩散的,但有相当数量的钙与膜和细胞溶胶的水不溶蛋白结合。因此,在总Ca++增加10倍的晶体中,结合的Ca++增加了2倍,近35%的Ca++在彻底透析(72小时)后仍然固定在水不溶性和膜蛋白上。相比之下,95%以上的钙在水溶性蛋白质组分中被透析去除。”

[Use of pyrimidine bases and ATP for conservative treatment of early cataracts] Larionov LN Oftalmol Zh, 1977, 32:3, 221-2.

[嘧啶碱基和ATP在早期白内障保守治疗中的应用]

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. “Abnormalities in glucose metabolism are thought to be among the main causes of cataract formation. 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 (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 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.

晶状体中吡啶核苷酸和黄蛋白的非侵入性测量,” Tsubota K;莱恩风湿性关节炎;Kenyon KR Invest Ophthalmol Vis Sci 28:5, 785- 9,1987。“葡萄糖代谢异常被认为是白内障形成的主要原因之一。作者对晶状体进行了无创生化测量,提供了有关晶状体上皮内葡萄糖代谢的信息。用氧化还原荧光法无创测量兔晶状体内还原吡啶核苷酸(PN)和氧化黄酮类蛋白(Fp)的自荧光随深度的变化。在晶状体上皮处检测到440nm处(360 nm处激发)和540nm处(460 nm处激发)的自荧光峰。8 mM戊巴比妥钠是一种已知的线粒体呼吸抑制剂,当应用于晶状体时,440 nm处的自荧光峰增加,540 nm处的自荧光峰减少。440nm的自荧光被认为来自于还原的吡啶核苷酸,而540 nm的自荧光来自于氧化的黄素蛋白。用戊巴比妥阻断晶状体呼吸可使PN/Fp在应用戊巴比妥3.5小时内增加3倍。

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 high levels of L-lactate and high ratios of L-lactate in the lens/L-lactate in the aqueous. 2. Immature cataractous lenses with anterior capsular/subcapsular opacity; intermediate levels of RTP, intermediate values for the sums of RTP, RDP, and AMP, high L-lactate levels, and intermediate values of the ratios of L-lactate in the lens/L-lactate in the aqueous.

老年白内障晶状体中某些核糖核酸、l -乳酸和丙酮酸的浓度与前囊/下囊混浊有关,”Laursen AB Acta Ophthalmol (coph) 54:6, 677-92,1976。“在白内障手术摘除的老年白内障晶状体中,测定了一些核糖核苷三磷酸和二磷酸、腺苷-5'-单磷酸、l -乳酸和丙酮酸的浓度。在15例老年白内障晶状体中,丙酮酸浓度可以忽略不计(中位数= 56 mumol/kg晶状体湿重)。根据老年白内障晶状体(N = 80)的生物显微镜外观与相关代谢物的浓度和比例之间的相关性,我们发现以下分类是合理的:1。未成熟白内障晶状体无前囊/囊下混浊:晶状体中有高水平的三磷酸核糖核苷(RTP)、高水平的三磷酸核糖核苷(RDP)、二磷酸核糖核苷(RDP)和腺苷5'-单磷酸腺苷(AMP),晶状体中有高水平的l -乳酸和高比例的l -乳酸/水溶液中l -乳酸。2. 未成熟白内障晶状体,前囊或下囊混浊;中间水平的RTP,中间值的RTP, RDP和AMP的总和,高的l -乳酸水平,中间值的l -乳酸在晶状体中的比率/水中的l -乳酸。

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.]

白内障患者晶状体的脂质荧光团[j]。[初期白内障的特征是脂肪酸自由基氧化产物的荧光。]

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