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)

The disposition and disposal of the -SH groups of the lens during aging and cataractogenesis have been investigated by laser Raman spectroscopy as a noninvasive microprobe in the intact living lens. In this procedure -SH and -S-S- give unique discrete Raman signals (at 2580 and 508 cm-1) that may be used to calculate relative concentrations in a very small volume of the lens. We present evidence showing an unexpected and remarkable difference with respect to these groups between the mouse lens and the lenses of guinea pig and man. The mouse lens nucleus exhibits a precipitous fall in the -SH concentration on aging from 1 to 6 months; concomitantly, there is a rise in -S-S- of comparable magnitude, indicating a direct conversion. The guinea pig lens, however, is quite different with respect to the age-dependent change in nuclear -S-S-: there is none between 6 months and 5 years. In the human lens -S-S- behaves exactly as in the guinea pig lens: the level is low and does not change with age between 9 and 65 years. With respect to nuclear -SH, these two latter species of lenses show some decrease with age but nothing like the approach to zero found in the aging mouse lens nucleus. These differences involving lenticular -SH and -S-S- appear to be correlated with the hard nucleus in the mouse lens and the softer nuclei of lenses in guinea pigs and humans. The relatively high level of -S-S- in the old but clear mouse lens does not support the idea that protein aggregation involving formation of intermolecular -S-S- bonds is necessarily an important cause of nuclear cataract. The small but significant age-related depression of -SH in guinea pig lens nuclei without any accumulation of -S-S- may be explained as a result of glutathione (GSH) oxidation and subsequent extrusion of glutathione disulfide (GSSG) by the lens. We propose that the oxidation of glutathione proceeds by reaction with protein disulfide groups to yield protein sulfhydryl (PSH) and a mixed disulfide of glutathione and protein; the mixed disulfide is capable of being reduced by glutathione reductase and NADPH, yielding the original PSH and GSSG, which is extruded from the lens. It remains to be determined if this mechanism is more active in guinea pig and human lenses than in the mouse lens.
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PMID:Disulfide bond formation in the eye lens. 386 9

1. Cataracts were developed by incubating rabbit lenses for 22hr. at 37 degrees in a culture medium containing tyrosine and tyrosinase (EC 1.10.3.1). 2. A 45% diminution in the content of GSH and significant inhibition of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) activity were observed in the cataractous lenses compared with controls. 3. GSSG accumulated in both cataractous and control lenses. Significant amounts of GSSG were transported outward from the cataractous lenses and small amounts from control lenses. 4. Transport of GSSG from rabbit lens incubated in a diffusate of plasma from a naphthalene-fed rabbit was also observed. 5. GSSG was found in the aqueous humour obtained between 2 and 24hr. after feeding of naphthalene to rabbits; subsequently the GSSG in the aqueous humour decreased to almost undetectable amounts in 48hr.; in controls, GSSG was not detectable. 6. A possible mechanism of formation of experimental and senile cataract is briefly discussed.
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PMID:Cataract produced by tyrosinase and tyrosine systems in rabbitens in vitro. 497 83

A new method has been developed for the conjugation of rat lens glutathione by 1-chloro-2,4-dinitrobenzene (CDNB). This reaction is catalysed by glutathione S-transferase present in the lens. One milliliter of 1 mM CDNB per two rat lenses conjugates more than 95% of the lens GSH in 30 min at 37 degrees. Lenses incubated with 1 mM CDNB for 30 min, followed by incubation in the culture medium without CDNB remained apparently clear for up to 24 hrs. The CDNB treated lenses were more susceptible to protein precipitation (cataract formation) when challenged with oxidants such as hydrogen peroxide and superoxide anions.
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PMID:Role of glutathione in the prevention of cataractogenesis in rat lenses. 629 3

Glutathione is present in both the reduced and oxidized form in the cornea, aqueous humor, ocular lens and retina. In these tissues it serves a variety of functions including maintaining normal tissue hydration (in the cornea) detoxifying peroxides and electrophilic compounds via enzymatic pathways and acting as a free radical scavenger to protect against photoinduced damage. In the ocular lens, glutathione levels decrease with aging and cataract formation. Recent evidence which may account in part for this phenomenon suggests that glutathione is altered when subjected to UV radiation in the presence of H2O2. Analyses employing fluorescence, phosphorescence, UV absorption and proton mode NMR spectroscopy demonstrate that UV exposure does alter both the reduced and oxidized forms of glutathione, producing the same final products. Moreover, while H2O2 speeds up the process, it is not essential to the reaction.
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PMID:Glutathione and ocular photobiology. 636 May 41

The mammalian lens contains an unusually high concentration of glutathione (GSH), the highest level being in the epithelium. GSH is present largely in the reduced state. The high concentration of GSH in a normal lens and the decreased concentration in most types of cataracts have led to many hypotheses on its role in cataract formation. These hypotheses are considered in the light of current evidence. GSH is synthesized and degraded in the lens. Both processes require ATP, derived largely from glycolysis. Carbohydrate metabolism is also involved in the maintenance of GSH in the reduced state. There is a direct link between the rate of formation of oxidized glutathione (GSSG) and the stimulation of the hexose monophosphate shunt through the generation of NADPH. One possible function of GSH in the lens is to maintain the thiol (SH) groups of proteins in the reduced state, thus preventing formation of high molecular weight (HMW) protein aggregates. The formation of HMW proteins in X-ray-induced cataracts through disulphide bond formation and the involvement of SH oxidation in HMW proteins isolated from human cataractous lenses suggest a role for GSH in protecting protein SH groups. GSH in the lens may also protect critical SH groups involved in regulating cation transport and permeability. Studies with mammalian lenses indicate that lowering the lens GSH concentration leads to increased permeability to cations and inactivation of Na+,K+-ATPase. A consequence of the changes in ion distribution is the inhibition of protein synthesis, which may explain the cessation of growth in cataractous lenses. GSH may also protect against oxidative damage to the lens. GSH metabolism is intimately involved in detoxification of H2O2, normally present in the aqueous humour. Lenses with impaired shunt activity or inhibited glutathione reductase are more susceptible to oxidative damage by peroxide. This may contribute to the formation of cataract.
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PMID:Metabolism and function of glutathione in the lens. 656 81

A dose of 20 mumol selenite/kg body weight is a potent and a very rapid inducer of cataracts in young rats. We investigated the rate at which physiological concentrations of selenite would catalyze the oxidation of glutathione in vitro and found that selenite was a strong sulfhydryl oxidant. To test if selenite had the same effect in vivo, the oxidation state of five kinds of lenticular sulfur were measured in suckling rats following a cataractous dose of selenite. The measurements included reduced glutathione (GSH), oxidized glutathione (GSSG), protein-bound glutathione ( PSSG ), reduced protein sulfhydryl ( PSH ), and oxidized protein sulfhydryl ( PSSP ). While selenite caused a 44% decrease in lens GSH by 6 days postinjection, there was no concurrent increase in either GSSG or PSSG . Likewise, there was no evidence for increased oxidation of PSH to PSSP . To determine if GSH loss were the cause of the selenite cataracts, we injected normal rats with the glutathione synthesis inhibitor buthionine sulfoximine (BSO). Lens GSH dropped more than 96% by 4 days post-BSO injection; however, no cataracts formed. Thus, selenite cataract does not appear to be caused by extensive sulfhydryl oxidation and cannot be attributed exclusively to GSH loss.
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PMID:State of sulfhydryl in selenite cataract. 672 15

Amounts of reduced, oxidized, and protein-bound glutathione (GSH) were measured in normal and cataractous lenses of pups and adult dogs. Lenses from pups included normal lenses from clinically normal pups, clear lenses from Beagle pups bred for glaucoma, and congenital cataractous lenses from Miniature Schnauzer pups. Lenses from adults included normal lenses from normal mixed-breed dogs, congenital cataractous lenses from Miniature Schnauzers, and complete mature cataractous lenses from clinical patients of different breeds. Glutathione in the normal lenses from pups and adult dogs is predominantly reduced GSH; oxidized GSH is about 2.1% to 2.6% of the reduced GSH values. The reduced GSH values are lower in normal pups [7.08 mumoles/g (wet wt) of lens] than in adults [7.83 mumoles/g (wet wt) of lens]; reduced GSH values decrease further in cataract formation. The decrease in oxidized GSH values parallel those of reduced GSH, except in the advanced cataracts of clinical patients in which oxidized GSH [0.045 mumoles/g (wet wt) of lens] was 9% of the GSH values. The GSH bound to soluble and insoluble lens proteins of congenital cataractous Miniature Schnauzer pups was significantly (P less than 0.01 and P less than 0.02, respectively) lower per gram of protein than that in pups with normal lenses. However, the soluble and insoluble protein-bound GSH of congenital cataractous lenses of adult Miniature Schnauzers and lenses in clinical patients with mature cataracts [based on mumole of GSH/g (wet wt) of lens] were not significantly different (P greater than 0.05) from that in adult dogs with normal lenses.
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PMID:Reduced, oxidized, and protein-bound glutathione concentrations in normal and cataractous lenses in the dog. 710 4

The direct effect of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] on rat crystalline lens was investigated in this study. 12(S)-HETE lowered the glutathione (GSH) level and GSH reductase activity in the lens, while accelerating aggregation and insolubilization of lens proteins and production of thiobarbituric acid-reactive substances. The study also indicated that 12(S)-HETE insolubilized alpha-crystalline and induced opacification of the lens when the lens was incubated with 12(S)-HETE. From the results, we presumed that 12(S)-HETE may be oxidized or peroxidized easily and automatically in the air. The substances derived from 12(S)-HETE by oxidation or peroxidation may give the action disordering lens normalcy and induced cataract formation. Thus, the direct effect of 12(S)-HETE may of no benefit to the crystalline lens.
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PMID:Direct effect of 12(S)-hydroxyeicosatetraenoic acid on rat crystalline lens is perturbation of lens normalcy. 749 88

Single viable fiber cells have been isolated from the cortex of rat ocular lens by proteolytic digestion of the intact lens in calcium-free media. In isomolar sucrose, the isolated cells maintain their fiber-shaped morphology and exclude trypan blue. The surface morphology of the isolated fiber cells appears to be largely unaffected by the isolation procedure. The concentrations of adenine nucleotides, GSH, GSSG and the rate of glycolysis in the isolated fiber cells were comparable to those in the cortex. Upon perfusion of the tissue chamber with Ringer's solution, the fiber cells undergo a series of transformations, beginning with cell swelling, periodic blebbing along the longitudinal cellular axis, and eventual disintegration of the fiber into a number of resealed globules or round cells which resemble light-scattering areas in human cortical and supranuclear cataract. This disintegrative globulization of the fiber cells appears to be mediated by calcium influx, as it was prevented or delayed by a reduction in extracellular calcium concentration, verapamil or lanthanum. Since disturbances in calcium homeostasis are associated with various forms of cataract, such Ca(2+)-mediated disintegrative globulization of the fiber cells may be responsible for the formation of light scattering centers during cataractogenesis.
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PMID:Calcium-mediated disintegrative globulization of isolated ocular lens fibers mimics cataractogenesis. 755 94

There are two approaches to the question of whether solar radiation contributes to human cataract. The first, epidemiological studies, investigates correlations between man's environmental UV dose and cataract frequency. The second, animal models, investigates the effects of varying UV strengths and spectra on lens opacification in vivo or in vitro. While the latter approach typically provides for direct evidence, the data must still be extrapolated to human lenses. Results of physiological studies suggest that UV photons interact with proteins of the epithelial cell membranes, in particular tryptophan residues, transport ATPases and cytoskeletal proteins. One hypothesis is that damage to ion pumps and channels accumulates over the years as repair processes incompletely restore membrane function. Peroxidative damage is likely in view of the formation of UV-induced lipid peroxides in the lens epithelial membranes. Loss of homeostatic control of ions, particularly Ca++, leads to crystallin disorder in small regions of the underlying fiber cells. In our diabetic cataract studies, intracellular Ca++ electrodes detected large shifts in intracellular Ca++ before bulk-lens changes were apparent. Similar occurrences likely characterize UV cataract. Our lab is one of few studying lens physiology and how it is altered following transient exposures to UV-B and UV-A, both of which pass through the cornea. Some changes include: loss of epithelial cell GSH; elevated Ca++; loss of membrane voltage; impaired transport of Na+; increased permeability to ions and water; inhibition of critical enzymes; and a decrease in the rate of membrane synthesis.
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PMID:A review of the evidence that ultraviolet irradiation is a risk factor in cataractogenesis. 763 90


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