Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured rabbit lenses were irradiated with UV (311 nm peak; 295-340 nm) for 30 to 60 min. The entire spectrum lies in the near-UV, the major component is UVB, with a minor portion (25%) of UVA, and is henceforth referred to as near-UV(B). Posterior irradiation caused no cataract and no significant ionic imbalances compared to anterior irradiation, which caused opacification and marked changes in sodium and calcium concentrations. Anterior irradiation also resulted in reduced Na/K-ATPase activity in the epithelium. ATPase activity was not immediately inhibited; rather, only after culture was enzyme activity reduced. The concentration of reduced glutathione (GSH) decreased rapidly in the epithelium and more slowly in the underlying lens fibers. Loss of GSH was more rapid and extensive when irradiation occurred in the presence of oxygen. Irradiation under anaerobic conditions resulted in opacification but was considerably less extensive than when irradiation of lenses occurred in the presence of 7% oxygen. Near-UV(B) damage following anaerobic irradiation and 20 hrs of culture resulted in an increase in sodium levels and loss of GSH; calcium levels were not significantly elevated. Since irradiation of tryptophan solutions produced small amounts of hydrogen peroxide, the possibility of hydrogen peroxide-mediated damage was investigated but no role could be substantiated. Peroxide detoxification by the epithelium of near-UV(B) cataracts was observed, as measured by its ability to eliminate hydrogen peroxide added as a bolus.
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PMID:Mechanisms involved in cataract development following near-ultraviolet radiation of cultured lenses. 132 94

The normal internal pH (pHi) of the amphibian lens, measured using ion-sensitive microelectrodes, is 7.1 (pHo = 7.4) and the membranes appear to be relatively impermeable to hydrogen ions. Perifusing the lens with 100% CO2 appeared to be the most efficient way of decreasing pHi, which fell to 6.3 after an exposure lasting 30 min. Accompanying this acidification, there was a rapid depolarization of membrane potential (Em), a decrease in membrane resistance (Rm) and increase in internal or bulk resistance (Ri). These changes did not occur if the external pH alone was decreased. All changes were reversible, although the time course of Ri recovery was faster than the others. The decrease in membrane resistance could be prevented if the chloride concentration in the external solution was reduced, suggesting that internal acidification opens chloride channels in the amphibian lens. Since chloride ions are normally close to equilibrium across amphibian lens membranes, it is suggested that the pH-induced depolarization is due to a decrease in potassium conductance. The increase in internal resistance on perifusing with CO2 is most likely due to a closing of gap junctions between the fibre cells. The relationship between internal conductance and pHi was very similar to that obtained in other tissues and could be fitted by the Hill equation with n = 6 and pK = 6.9. Fibre junctional conductance seems sensitive to small changes in hydrogen ion concentration around the resting pH. Two agents, aspirin and cyanate, that are believed to influence cataract development, slowed the recovery of Em, Rm and Ri during recovery from an acid load.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Internal acidification modulates membrane and junctional resistance in the isolated lens of the frog Rana pipiens. 154 38

The ability of transparent and cataractous human, rabbit and mice lenses to metabolize hydrogen peroxide in the surrounding medium was evaluated. Using a chemiluminescence method in a system of luminol-horseradish peroxidase and a photometric technique, the temperature-dependent kinetics of H2O2 decomposition by lenses were measured. The ability of opaque human lenses to catalyze the decomposition of 10(-4) M H2O2 was significantly decreased. However, this was reversed by the addition of GSH to the incubation medium. Incubation of the mice lenses with the initial concentration H2O2 10(-4) M led to partial depletion of GSH in normal and cataractous lenses. Human cataractous lenses showed decreased activities of glutathione reductase, glutathione peroxidase (catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids), superoxide dismutase, but no signs of depletion in activities of catalase or glutathione peroxidase (utilizing H2O2). The findings indicated an impairment in peroxide metabolism of the mature cataractous lenses compared to normal lenses to be resulted from a deficiency of GSH. An oxidative stress induced by accumulation of lipid peroxidation products in the lens membranes during cataract progression could be considered as a primary cause of GSH deficiency and disturbance of the redox balance in the lens.
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PMID:Peroxide-metabolizing systems of the crystalline lens. 173 65

Conditions of oxidative stress may lead to cataract formation. Reaction of certain flavoproteins, the NADH: oxidoreductases, with different quinones is well known to form hydrogen-peroxide. This reaction was investigated to get more information on cataract induction by naphthalene and its quinone metabolites. Protein extracts from bovine lens cortex exhibit "diaphorase" activity, indicated as dye reduction in the presence of NADH and dichlorophenol-indophenol (DCPIP) or ferricyanide. Different redox cycling compounds are shown to be active in this "diaphorase" reaction by lens protein extract (LCE): Oxygen consumption can be detected in the presence of pyrroloquinoline quinone and juglone whereas 1,4-naphthoquinone, menadione and paraquat are no redox cyclists in this flavoprotein catalyzed reaction.
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PMID:Cataract induction by 1,2-naphthoquinone. I. Studies on the redox properties of bovine lens proteins. 187 11

The concentrations of hydrogen peroxide in the aqueous humor and urine of several animal species and humans have been determined. The determinations are based on peroxide-dependent decarboxylation of I-[14C]-alpha-ketoglutaric acid and measurement of the resulting 14CO2 by quantitating the radioactive disintegration. The levels of H2O2 in most animals varied between 5.0 and 41 microM for aqueous, and 115 and 187 microM for urine. The levels of peroxide in the urine of steer, cat and baboon were lower and fell out of the above range. In the aqueous of humans with cataracts, the levels ranged from 33 to 324 microM, the overall average being 189 +/- 88 microM. The source of such high levels in the aqueous of cataract patients is currently being studied.
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PMID:Radio-isotopic determination of hydrogen peroxide in aqueous humor and urine. 193 85

Human cataract lens proteins can be bleached by exposure to sodium borohydride (NaBH4), sodium cyanoborohydride (NaCNBH3), or hydrogen peroxide (H2O2). The decolouration resulting from these treatments could be monitored by a change in absorbance at 350 nm. At pH 12 the magnitude of the absorbance change increased in proportion with the severity of the nuclear cataract in the case of NaBH4 and H2O2 treatments, but not in the case of NaCNBH3 treatment. The rate of change in absorbance at 350 nm following exposure to the different reagents was used to evaluate three model systems for senile nuclear cataract. These model systems utilized calf lens proteins which had been tanned by exposure either to 3-hydroxyanthranilic acid, dopa/tyrosinase, or ultraviolet light.
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PMID:Decolouration of the lens pigment in senile nuclear cataract. 212 39

We examined the mechanism of endothelial injuries in the inherited cataract rats (ICR), which have a number of age-associated spontaneous injuries in the aortic endothelium. Cell cycle traverse rate of endothelial cells of ICR was shorter than that of Wistar rats. The rate was estimated from bromodeoxyuridine (BrdU) incorporation into cell nuclei measured periodically after BrdU pulse labeling. Next we established the method for measurement of cultured endothelial cell injury by neutrophils with flow cytometry by assessing the regeneration of injured endothelial cells. By the use of the gate analysis method, contaminated neutrophils were excluded from the analysis. Endothelial cell injury by neutrophils of Wistar rats was detectable at 1 x 10(5) neutrophils (1 neutrophil to 1 endothelial cell) when stimulated with 10 ng/ml phorbol myristate acetate (PMA). Extent of injury increased with an increasing number of neutrophils and the concentration of a stimulator, PMA. We detected endothelial cell injury by ICR neutrophils not only when they were stimulated but also in a resting condition, and ICR neutrophils yielded more injury than Wistar rat neutrophils. Number of adhered neutrophils to endothelial cells and effects of plasma or lymphocytes were the same between two strain rats. Scavengers of hydrogen peroxide and singlet oxygen inhibited the ICR neutrophil-induced endothelial cell injury. These findings indicate that an increase of generation of excited oxygen species from neutrophils, particularly of singlet oxygen, may cause injury of endothelial cells in this specific strain of rats.
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PMID:Flow cytometric study of injuries in cultured endothelial cells by neutrophils of the inherited cataract rats. 217 89

This paper presents an overview of the current state of our knowledge concerning the metabolism and function of glutathione (GSH) in the lens, with particular reference to the contributions of Dr Jin H. Kinoshita to this field. Glutathione in the lens is synthesized from its constituent amino acids and degraded by mechanisms involving transpeptidation and hydrolysis. The turnover of GSH in the lens is due to its catabolism rather than transport of GSSG as is the case in red blood cells and some other tissues. Three aspects of the functional role of GSH in cataract formation are considered. First, GSH may be important in maintaining protein thiols in the reduced state, thus preventing the formation of high molecular weight protein aggregates which are the basis for light scattering and lens opacification. A second function may be to protect membrane -SH groups that are important in cation transport and permeability. A third functional role is to detoxify hydrogen peroxide and other organoperoxides. The glutathione redox cycle is intimately involved in the detoxification of H2O2 which is normally present in the aqueous humor.
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PMID:Glutathione and its function in the lens--an overview. 219 12

Intact rat lenses were incubated in riboflavin-containing Tyrode solution or medium-199, generating photochemically active species of oxygen and the oxidative stress measured in terms of the decrease in active accumulation of rubidium, and the fall in the levels of glutathione and ATP. Addition of pyruvate to the medium prevented the tissue against oxidative damage as evidenced by a greater accumulation of rubidium and higher levels of glutathione and ATP. Pyruvate was thus found to be effective against the toxicity of oxygen derivatives, particularly the hydrogen peroxide. In dark experiments also, conducted in glucose-free medium, the uptake of rubidium was substantially greater in the presence of pyruvate. The levels of ATP were also higher. These results, therefore, suggest that this ketoacid is beneficial to the tissue through its ability to decompose H2O2 as well through providing a metabolic support. The development of in vitro cataract under the photochemical effects of riboflavin and oxygen was also effectively thwarted by pyruvate. The results are thus potentially useful from the point of view of developing pyruvate and similar compounds as effective anticataract agents.
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PMID:Photoinduction of cataracts in rat lens in vitro. Preventive effect of pyruvate. 237 72

We determined the conditions required for the establishment of lens epithelial cell lines from individual Emory and age matched cataract-resistant (CR) mice, and investigated the response of these cells to hydrogen peroxide. The technique described here permits the establishment of mouse lens epithelial cell lines from individual animals and provides an opportunity to study changes in epithelial function that precede and accompany cataract formation and aging. Capsules with lens epithelial cells were isolated from 1, 6 month, and 1.5-2 year old Emory and CR mice and cultured in minimal essential medium (MEM) containing 4% heat inactivated fetal bovine serum and 4% heat inactivated rabbit serum. Seeding efficiency at 3 hours was approximately 83% for all lines, doubling time was 22-24 hours, and the shape of the growth curves was comparable for Emory and CR mice from each age group. A three hour exposure of Emory and CR mouse lens epithelial cells from older animals to a constant level of 0.02 mM hydrogen peroxide or to an initial concentration of 0.01, 0.03, or 0.05 mM hydrogen peroxide resulted in a delay in growth. The delay in cell proliferation was decidedly more pronounced in lens epithelial cells from Emory mice. Lens epithelial cells from cataractous mice appear to be more sensitive to oxidative insult than their CR counterparts.
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PMID:Establishment of lens epithelial cell lines from Emory and cataract resistant mice and their response to hydrogen peroxide. 248 78


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