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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid peroxidation has been shown to be involved in the pathogenesis of some types of cataract. The possibility of such a mechanism was investigated in Emory mouse cataract. Malondialdehyde, a breakdown product of lipid peroxides, increased 4-fold in advanced cataract. Studies on cation transport revealed that in early cataract there was no alteration in permeability and active transport of cations. However, these functions were significantly altered in advanced cataract as evidenced by about 300% increase in cellular influx of 22Na+ (140 mM) and 50% fall in cellular uptake of 86Rb+ (5 mM). At this stage of cataract, the ouabain- inhibitable component of uptake of Rb+ was drastically decreased, whereas the ouabain-resistant component was unchanged. The mannitol-space increased markedly with progression of cataract. Altered transport of cations in cataract was indicative of damaged membranes which may be due to peroxidation of unsaturated fatty acids in the lipid bilayers concomitant with oxidation of sulfhydryl groups of proteins of the plasma membrane. Superoxide dismutase, catalase and glutathione peroxidase, the defensive enzymes against reactive species of oxygen, were decreased 54%, 57% and 62% respectively in cataract, exposing the lens to oxidants such as 02(-), H202, 0H. and 1 delta 02, which can initiate lipid peroxidation and/or oxidation of protein.
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PMID:Increased lipid peroxidation and altered membrane functions in Emory mouse cataract. 718 12

This review examines the hypothesis that oxidative stress is an initiating factor for the development of maturity onset cataract and describes the events leading to lens opacification. Data are reviewed that indicate that extensive oxidation of lens protein and lipid is associated with human cataract found in older individuals whereas little oxidation (and only in membrane components) is found in control subjects of similar age. A significant proportion of lenses and aqueous humor taken from cataract patients have elevated H2O2 levels. Because H2O2, at concentrations found in cataract, can cause lens opacification and produces a pattern of oxidation similar to that found in cataract, it is concluded that H2O2 is the major oxidant involved in cataract formation. This viewpoint is further supported by experiments showing that cataract formation in organ culture caused by photochemically generated superoxide radical, H2O2, and hydroxyl radical is completely prevented by the addition of a GSH peroxidase mimic. The damage caused by oxidative stress does not appear to be reversible and there is an inverse relationship between the stress period and the time required for loss of transparency and degeneration of biochemical parameters such as ATP, GPD, nonprotein thiol, and hydration. After exposure to oxidative stress, the redox set point of the single layer of the lens epithelial cells (but not the remainder of the lens) quickly changes, going from a strongly reducing to an oxidizing environment. Almost concurrent with this change is extensive damage to DNA and membrane pump systems, followed by loss of epithelial cell viability and death by necrotic and apoptotic mechanisms. The data suggest that the epithelial cell layer is the initial site of attack by oxidative stress and that involvement of the lens fibers follows, leading to cortical cataract.
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PMID:Oxidative stress-induced cataract: mechanism of action. 767 10

We investigated the effect of alpha-lipoic acid, a powerful antioxidant, on cataract formation in L-buthionine(S,R)-sulfoximine (BSO)-treated newborn rats and found that a dose of 25 mg/kg b.w. protected 60% of animals from cataract formation. L-buthionine(S,R)-sulfoximine is an inhibitor of glutathione synthesis, whose administration to newborn animals leads to the development of cataracts; this is a potential model for studying the role of therapeutic antioxidants in protecting animals from cataract formation. Major biochemical changes in the lens associated with the protective effect of alpha-lipoic acid were increases in glutathione, ascorbate, and vitamin E levels, loss of which are effects of BSO administration. Treatment with alpha-lipoic acid also restored the activities of glutathione peroxidase, catalase, and ascorbate free radical reductase in lenses of L-buthionine(S,R)-sulfoximine-treated animals but did not affect glutathione reductase or superoxide dismutase activity. We conclude that alpha-lipoic acid may take over some of the functions of glutathione (e.g., maintaining the higher level of ascorbate, indirect participation in vitamin E recycling); the increase of glutathione level in lens tissue mediated by lipoate could be also due to a direct protection of protein thiols. Thus, alpha-lipoic acid could be of potential therapeutic use in preventing cataracts and their complications.
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PMID:Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats. 775 Aug 5

Oxidative mechanisms are thought to play a major role in several biological phenomena, including cataract formation. In the following studies we determined the relative levels of expression of the genes for the mRNAs for glutathione peroxidase (GPx), glutathione reductase (GR), CuZn-superoxide dismutase (CuZn-SOD) and catalase, in both the rat lens and liver. Northern blot hybridization methods were used to determine the mRNA size. The RNase protection method was used to determine levels of expression for these mRNAs plus levels of expression for alpha A-crystallin and gamma-crystallin mRNAs in the lens, and gamma-actin mRNAs in both the lens and the liver; using [32P]-labeled specific cRNA probes transcribed from the various cDNA clones for the mRNAs being studied. The data was normalized relative to the level of expression of alpha A-crystallin and gamma-actin mRNAs in the lens, and to gamma-actin mRNA in the liver. We find the levels of the mRNAs in the lens fall in the following descending order: GPx > GR > CuZn-SOD > catalase, in the same order as has been reported for the activities of the enzymes in the lens. In the liver, levels of these mRNAs were as follows: GPx > CuZn-SOD > GR > catalase. In the liver, CuZn-SOD mRNA was expressed at about four times the level found in the lens, GPx at three times, catalase at three times and GR at about the same level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Levels of expression of the genes for glutathione reductase, glutathione peroxidase, catalase and CuZn-superoxide dismutase in rat lens and liver. 783 6

The activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) and free radicals were measured, and the morphological changes were observed in the lens of control rats, selenium-deficient (SeD) and/or vitamin E deficient (VED) rats. The activities of GSH-Px in the lens of SeD rats decreased significantly. The GSH-Px activities of lens were positively related to erythrocytes selenium level. There was a free radical at g = 2.0015 in the rat lens of all groups, but the content of free radicals in the lens of SeD group was significantly higher than that of the control group. The free radical content of lens was negatively related to erythrocytes selenium level, as well as the GSH-Px activities in the lens. In vitro, ultraviolet radiation caused the generation of another kind of free radical (g = 2.0097) in the lens of all groups, but the amount of the free radical in the lens of the SeD group was also significantly higher than that of the control group. The activities of SOD and GSSG-R in VED rat lens were significantly decreased. The amount of MDA in the lens of SeD and/or VED rats were significantly increased. The results showed that the decrease of antioxidative capability in the lenses of SeD and/or VED rats accelerated the lipid peroxidation and generation of free radicals. Although only early morphological changes in SeD and/or VED rat lens were observed, it is considered that selenium and vitamin E deficiency may be involved in the occurrence of cataract.
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PMID:Biochemical and morphological changes in the lenses of selenium and/or vitamin E deficient rats. 794 5

The relationship between the activity of the antioxidant defense enzyme glutathione peroxidase (GSH-PX) and the degree of cataract (lens opacity) was examined in 14 Emory mice at the age of 2, 7 and 10 months. Significant decreases in specific GSH-PX activity (mU/mg wet tissue) in the lens as well as in the residual eye tissue were found between 2 and 10 months of age, showing a highly significant correlation of this decrease (r = 0.590, p approximately 0.001) with the increasing degree of turbidity of the lenses. The results are discussed with regard to the changes of antioxidant mechanisms during cataractogenesis and aging. The role of the maintenance of an optimal level of GSH-PX and other well-known antioxidants (enzymes, vitamins, trace elements including iodide) for a delay of cataractogenesis is pointed out.
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PMID:[Changes of Glutathione Peroxidase Activity in Eye Tissues of Emory Mice in Relation to Cataract Status and Age]. 814 88

61 spa patients, predominantly with heart and vascular diseases, were divided into 2 therapeutic groups. In addition to the usual balneotherapeutic program, one group (J) received a course of "iodine brine concentrate" for drinking (2 x 100 ml, daily iodine uptake approximately 9 mg), and the control group (CI) received isotonic NaCl in the same way. The patients were mostly on a reduced-fat and -calorie diet. The following parameters were determined at the beginning and at the end of the 26-day treatment period: total cholesterol, HDL-cholesterol, triglycerides, lipoprotein (a) (in serum); selenium (Se), malondialdehyde (MDA), and activities of Se-dependent, Se-independent, and total glutathione peroxidase (GSH-PX) (in plasma). In the J group, a significant increase was found in Se-independent (+17%) and total GSH-PX (+5%) and a significant decrease in total cholesterol (-6.9%) and MDA (-13.2%). At the end of the cure, Se levels were higher in the J group than in the C1 group. The only significant change in the C1 group was a decrease in HDL-cholesterol. Positive correlations were found between selenium and Se-dependent GSH-PX (r = 0.253) and between total GSH-PX and Se-dependent GSH-PX (r = 0.665). A negative correlation was obtained between Se-dependent and Se-independent GSH-PX (r = -0.331). The results are discussed with regard to the importance of antioxidant defense mechanisms in several degenerative diseases (atherosclerosis, diabetes, cataract etc.), and also respecting interactions between iodine and selenium metabolism, as well as normalization effects conditioned by the balneotherapy itself.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Changes in selenium status, antioxidant enzyme activity and lipid peroxide level after drinking cures in Bad Hall health resort]. 814 96

Previous work has demonstrated that photochemically induced oxidative stress generated with 4 microM riboflavin in a 4% oxygen atmosphere utilizing daylight type radiation is capable of causing cataract in cultured rat lenses. Such cataract is prevented by the GSH peroxidase type mimic, AL-3823A. Examination of the early stages of cataract formation produced by short-term oxidative stress and recovery is now reported. A 24-hr oxidative stress, under the above conditions, causes loss of transparency, particularly in the equatorial region, increased hydration, loss of glyceraldehyde-3-PO4 dehydrogenase activity, oxidation of non-protein thiol and a decrease in 86Rb and [14C]choline uptake and ATP levels. Examination of recovery of these parameters during a 72-hr period indicates, in most cases, little or no reversal of oxidative damage. Hydration and loss of non-protein thiol continued during the recovery period. The presence of AL-3823A during the stress period prevented change in all parameters. Transport systems appear to be particularly vulnerable to this type of oxidative stress losing 50% or more activity within 4 hr. Even after a 2-hr stress, choline transport did not recover even though, under these conditions, ATP levels had only decreased slightly. Cytosolic components such as non-protein thiol and glyceraldehyde-3-PO4 dehydrogenase also showed little change after a 4-hr insult. 86Rb efflux experiments indicated no change in permeability during a 24-hr stress period. The overall conclusion from these studies is that a 24-hr oxidative stress which appears to reflect physiological conditions existing during cataract development, causes extensive, irreversible damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The prevention of cataract caused by oxidative stress in cultured rat lenses. II. Early effects of photochemical stress and recovery. 815 19

In the anterior segment of the mammalian eye, the ocular ciliary epithelium produces the aqueous humor, a fluid that nourishes and protects the avascular tissues from oxidative stress. This report details the results of a study of molecular cloning, sequencing, and expression of plasma glutathione peroxidase (GPx-P) from the bovine ocular ciliary epithelium. The bovine GPx-P cDNA contains an open reading frame of 226 amino acids with a calculated molecular weight of 24,860. The corresponding amino acid sequence showed an overall identity of 88% with the human GPx-P, 88.5% with the rat GPx-P, and 46.4% with the cellular bovine glutathione peroxidase (GPx-1). The levels of GPx-P and GPx-1 transcripts in ocular tissues were analyzed and the ciliary epithelium was found to express the highest levels of GPx-P transcripts in human and bovine eyes, whereas the cornea of calf eyes expressed the highest levels of GPx-1 transcripts. Surprisingly, the lens, on which oxidants have profound effects leading to cataract formation, expressed the lowest levels of GPx-P and GPx-1 transcripts in human donor eyes. These results provide new evidence of differential gene expression of the GPx-P and GPx-1 forms in the mammalian eye and stresses the functional role of the ocular ciliary epithelium in protecting the anterior segment of the eye from oxidative damage.
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PMID:Cloning of the bovine plasma selenium-dependent glutathione peroxidase (GP) cDNA from the ocular ciliary epithelium: expression of the plasma and cellular forms within the mammalian eye. 826 11

Oxidative stress is known to cause cataracts in lens culture systems and is believed to be an important factor contributing to human cataracts. In this communication, it is demonstrated that cataract development of cultured rat lenses produced as a result of photochemically induced oxidation in a 4% oxygen atmosphere similar to the native environment of the lens can be blocked by the transition metal complex AL-3823A. In this system, riboflavin is added to the medium as a photosensitizer. AL-3823A acts primarily as a glutathione peroxidase mimic, which catalytically metabolizes H2O2 and also has low superoxide dismutase-like activity. Measurements of H2O2, O2.-, and OH. indicate that appreciable levels of the first two of these oxidants and low levels of OH. are produced by this photochemical stressing system. The H2O2 concentrations are similar to those found in some patients with cataracts. The development of cataracts was followed over a 96-hr period. Transparency, hydration, glyceraldehyde-3-phosphate dehydrogenase activity, and protein and nonprotein thiol were monitored. All parameters show marked changes during the 96-hr period. However, in the presence of 200 microM AL-3823A, no difference between control and light-exposed lenses was observed with respect to these parameters. The results suggest that in vivo human cataract development caused by oxidative stress may be prevented by compounds of this type.
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PMID:Photochemically induced cataracts in rat lenses can be prevented by AL-3823A, a glutathione peroxidase mimic. 835 43


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