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)

It was reported previously that dietary ascorbate (ASC) delays the development of galactose-induced cataract in guinea pigs compared to the rate which is observed in ASC-deficient animals. Experiments were conducted to explore the possible mechanism of this phenomenon. Guinea pigs were fed for a period of up to 4 weeks either a normal diet (1 g ASC/kg diet) or a scorbutic diet (< 0.04 g ASC/kg diet) combined with 10% galactose in the drinking water. After 2 weeks, levels of ASC in animals on the scorbutic diet decreased by 95% in the aqueous humor and by 78% in the lens. Slit lamp examination showed that galactose-induced vacuoles in the lens equator formed at a significantly faster rate in the scorbutic animals. However, examination of biochemical parameters in whole lenses of the two groups of animals after 2 weeks showed no significant differences with regard to accumulation of galactose and galactitol, decreases in the levels of myoinositol, taurine and GSH or changes in cation concentrations. In order to examine possible regional changes in the lenses, various parameters were studied in the lens capsule-epithelium. On day 4, the capsule epithelia of scorbutic animals on a galactose diet had a content of galactitol two-and-a-half times higher than that of normal galactose-fed animals. Scorbutic conditions also intensified the loss of Na(+)-K+ ATPase activity in the lens capsule-epithelium caused by galactose feeding. Oxidized glutathione was not detectable in the lens capsule epithelia of any of the animals studied. Hexose monophosphate shunt activity was elevated in lenses of normal galactose-fed animals during the first hour of culture after death whereas lenses of scorbutic galactose-fed animals were not. Consistent with the in vivo findings, galactitol accumulation in dog lens epithelial cells exposed to 30 mM galactose was significantly inhibited by the presence of either ASC or dehydroascorbate (DHA) in the medium. Hexose monophosphate shunt activity in the cells was stimulated to two-and-a-half times its initial level by either 1 mM DHA or 30 mM galactose and slightly more than three-fold by a combination of the two challenges. The results suggest that decreased polyol accumulation in the lens epithelium of the normal galactose-fed guinea pig, which has a high level of ASC in the aqueous humor, accounts for the delay in onset of cataract compared to that for the ASC-deficient animal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A physiological level of ascorbate inhibits galactose cataract in guinea pigs by decreasing polyol accumulation in the lens epithelium: a dehydroascorbate-linked mechanism. 815 13

Based on previous findings that lens pigments and melanins share many physicochemical properties, human lens pigments and natural (hair) and synthetic melanins were submitted to oxidation with permanganate under strong acidic conditions. This procedure has been utilized for the characterization of melanins and results in the well defined products, thiazole-4,5-dicarboxylic acid (TDCA) and pyrrole-2,3,5-tricarboxylic acid (PTCA), which can be quantitated by high performance liquid chromatography (HPLC). PTCA is regarded as a marker of black eumelanins and was therefore a main component of synthetic DOPA-eumelanin and dark hair. Its identity was established by synthesis from 5-hydroxyindole-2-carboxylic acid. TDCA derives from pheomelanins and was therefore an important component of red hair and synthetic GSH-pheomelanin. TDCA was identified by its retention time relative to PTCA. The analysis of a series of cataract digests of increasing pigmentation (type I < type IV < type V) and a purified fraction of lens pigments (DE52 pigment) revealed the presence in these preparations of both PTCA and TDCA. The concentration of TDCA significantly increased with the degree of pigmentation of the digests and reached a maximum in the DE52 pigment. The TDCA/PTCA ratio was high in the lens preparations and comparable to that given by hair pheomelanin. These findings support that pheomelanin is an integral part of lens pigments. By comparing the yields of TDCA in GSH-pheomelanin and in the purified lens pigment, a 9% contribution of pheomelanin to the lens pigment was estimated.
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PMID:Melanins and lens pigments: a comparative study. 821 Feb 84

Oxidative stress has long been speculated to play an important role in cataractogenesis. In the H2O2-induced cataract model, rat lens showed extensive biochemical damage but very mild morphological changes after being exposed to H2O2 (0.5 mM) for 24 hr in culture. This damage included reduced glutathione (GSH) depletion, protein-GSH mixed disulfide (PSSG) elevation but not protein-protein disulfide (PSSP) formation. In order to understand the role of protein-thiol mixed disulfide formation in relation to the sequence of events during cataract induction, we conducted a long term H2O2 exposure study for up to 96 hr to monitor the dynamic changes in GSH and PSSG levels, the formation of PSSP aggregate, protein solubility, and the progression in lens opacity. Rat lenses were cultured in 0.5 mM H2O2 and harvested at intervals of 24, 48, 72 and 96 hr for the examination of morphological and biochemical changes. Contralateral lenses cultured in H2O2-free media were used as controls. It was found that the lenses had only patchy opacity at the equator after 24 hr, but became hydrated suddenly at 48 hr (31% heavier than the control), with an opacity which involved the entire outer cortical region. By 72 hr incubation, the nucleus was opacified. Lens GSH progressively decreased with time of H2O2 exposure, 40% was lost by 24 hr and over 95% by 48 hr. There was a concomitant elevation of PSSG, 16-fold over the controls by 24 hr and 45-fold by 48 hr followed by a decline to 34-fold after 72 hr. In addition, the level of protein-cysteine mixed disulfide (PSSC) was elevated after 48 hr incubation in H2O2. At this time point, PSSP aggregates began to appear both in water soluble (WS) and urea soluble (US) fractions along with a drastic reduction in protein solubility. Western blot analysis of the protein fractions identified beta and gamma, but not alpha-crystallin in the disulfide-containing aggregates. The lens clarity and biochemical changes partially recovered if the oxidant was removed within 24 hr, indicating a potential therapeutic role for antioxidants. The complete normalization of PSSG level under this recovery condition signifies that cells may have a natural defense system for controlling PSSG elevation.
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PMID:The effect and recovery of long-term H2O2 exposure on lens morphology and biochemistry. 840 82

The effect of glutathione (GSH) isopropyl ester on the progression of X-ray-induced cataract was investigated in rats. Intraperitoneal administration of 20 mg/kg GSH isopropyl ester, three times weekly, 1 day after a single irradiation dose delayed the progression of X-ray-induced cataracts significantly. The amount of non-protein SH groups and the Na+/K+ ratio in the lenses of drug-treated rats were maintained at the normal levels even 27 weeks after irradiation. Posttreatment with the drug resulted in a significantly lower level of malondialdehyde in the irradiated lenses than in the nontreated lenses. When 500 mg/kg GSH-isopropyl ester was administered by i.p. injection to normal rats, the GSH-ester was detected in plasma and aqueous humor after 15 min. In the lenses of the GSH-isopropyl ester-injected rats, the GSH level was 120% of that in the non-treated rats after 4 h, suggesting that GSH-isopropyl ester is transported from the aqueous humor to the lens and there converted to GSH after about 4 h. Our observations lead us to conclude that the delay of X-ray-induced lens opacity progression is due to maintenance of normal lenticular GSH levels achieved by post-irradiation administration of GSH-isopropyl ester. However, continuous administration of 100 mg/kg after irradiation had no effect on the progression of cataracts induced by X-rays.
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PMID:Glutathione isopropyl ester (YM737) inhibits the progression of X-ray-induced cataract in rats. 844 22

Supplementation of cyanate in rats caused a significant decrease in serum GSH and increase in calcium and phosphate level both in serum and lens. Consequently, these changes led to induce acidosis uremia in serum and hypercalcemia and hyperphosphatemia in lens which may be possible causing factor for cataract.
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PMID:In vivo effect of cyanate on serum and eye lens in rat. 850 Aug 20

The process of ageing in the normal human eye lens is unique among tissues due to the absence of turnover in the structural proteins. These proteins accumulate a variety of modifications throughout their lifetime. Significantly, the cysteine residues are subject to disulfide formation with the low molecular weight thiol compounds present in the lens. It has been shown that accumulation of glutathione and cysteine mixed disulfides in the proteins of normal human lens is a function of age. In this report a third mixed disulfide species gamma-glutamylcysteine (gamma-Glu-Cys), has been identified by comparison with standards which were produced through two distinct methods. This new mixed disulfide is only prominent in old lenses (> 60 years) and cataractous lenses. In these situations its level may approach those of cysteine mixed disulfide. The appearance of gamma-Glu-Cys may be coincident with biochemical abnormalities preceding cataract formation. This protein modification may be a result of changes in the GSH biosynthetic pathway within the lens.
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PMID:A new mixed disulfide species in human cataractous and aged lenses. 850 50

The effect of ultraviolet B (UV-B) radiation and a vitamin-C-deficient (VCD) diet on guinea pig lenses was investigated. The initial lens changes in the VCD group were observed by slit-lamp examination 6 weeks after the start of the VCD treatment; after 12 weeks the changes in the posterior subcapsular region became more prominent, and the dissociation around the posterior suture became wider and slightly deeper toward the posterior cortex. The high concentration of lens oxidized glutathione (GSSG), and the low ratio of reduced glutathione (GSH) to oxidized glutathione (GSH/GSSG) on the lens posterior region correlated with density changes in the corresponding layers as measured by Scheimpflug images with linear microdensitometry. It is suggested that the strong oxidative stress of the VCD diet caused the damage at the posterior part of the lens. UV-B radiation appeared to accelerate cataract progression in lenses that lack vitamin C.
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PMID:Morphological and biochemical changes in lenses of guinea pigs after vitamin-C-deficient diet and UV-B radiation. 853 97

In order to develop an effective screening model for anticataract agents, we examined the age dependence of cataract induction by glucocorticoid in developing chick embryos. Hydrocortisone sodium succinate (0.25 mumol) was administered to chick embryos on day 15 (15-day-old) and cataract formation was examined 48 hr later. Administration earlier than on day 13 or later than on day 15 was a little or ineffective. These results indicate that the formation of glucocorticoid-induced cataract in developing chick embryos depends on developing stages. The embryos treated with hydrocortisone sodium succinate on day 15 decreased GSH amount in the lens, approximately 50% of the control in 48hr. However, the embryos treated at other ages, in which cataract was not induced, showed little or no decrease of GSH. The cataract formation in chick embryos appeared to depend on structure of steroid and was due to biological activities of glucocorticoids. Since cataract is easily produced in a reproducible manner with high incidence by glucocorticoid, our chick embryo model will be a valuable model system for screening anticataract agents.
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PMID:Glucocorticoid-induced cataract of developing chick embryo as a screening model for anticataract agents. 857 17

A sensitive, electrochemical method was employed for the simultaneous measurement of reduced and oxidized glutathione in lens cortex, nucleus and capsule epithelia of rabbit lenses, normal human lenses and human cataracts. In addition, aqueous humor from cataract patients was also analyzed. The level of GSSG in the nucleus of human cataracts was significantly higher than that in the nucleus of normal eye bank lenses. The capsule epithelium of intracapsular extracted cataracts possessed high levels of reduced glutathione, despite the fact that much of the glutathione in the cortex and nucleus of the lenses was depleted. Levels of GSH in the aqueous humor of cataract patients were several times higher than those reported for normal aqueous humor. Electrochemical detection proved to be a useful technique for analysis of reduced and oxidized glutathione in lens and aqueous humor, especially when sample size is small, such as for capsule epithelium.
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PMID:Simultaneous measurement of reduced and oxidized glutathione in human aqueous humor and cataracts by electrochemical detection. 857 65

Lipid peroxidation (LPO) is a causative factor of cataract. The increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides) and end fluorescent LPO products, were detected in the lipid moieties of the aqueous humor samples obtained from patients with senile and complicated cataracts as compared to normal donors. The degrees of lens clouding were assessed quantitatively by measuring the optical density indices and areas of equidensities using digital image analysis. Human cataractous lenses showed decreased activity of glutathione peroxidase (GPX, catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids). The apparent Km for tert-butylhydroperoxide was 0.434 mM for human normal and cataractous lens GPX. When lenses were exposed for 1 h at 37 degrees C to linoleic acid hydroperoxide (LOOH, 0.5 mM) or egg phosphatidyl-choline hydroperoxide (PLOOH, 1 micro mol per 112 micro mol of phospholipid) in liposomes suspended in the incubation medium, normal, immature and mature human cataractous lenses showed a significant loss in the residual content of liberated LOOH to 62%, 38% or 17%, correspondingly, but little or no reduction was observed with PLOOH in liposomal membranes. Human, rabbit or mice transparent or immature cataractous lenses induced significantly more absorbance changes in conjugated diene, iodometric and TBA-reactive substance measurements when incubated with liposomal membranes which were decreased in the presence of free radical scavengers and antioxidant enzymes (EDTA, SOD, L-carnosine, chelated iron, catalase). Injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing LPO products induced the development of posterior subcapsular cataract. Saturated liposomes did not cause clouding of the lens. This modelling of cataract was accompanied by accumulation of fluorescing LPO products in the vitreous body, aqueous humor and the lens and also by a fall in the concentration of GSH in the lens. The peroxidative damage to the lens cell membranes and biomolecules induced in the lack of reductive detoxification of phospholipid hydroperoxides is proposed as the triggering mechanism of cataractogenesis.
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PMID:Failure to withstand oxidative stress induced by phospholipid hydroperoxides as a possible cause of the lens opacities in systemic diseases and ageing. 860 75


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