UMLS:C0086543 - FACTA Search

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

The Shumiya cataract rat (SCR) is a hereditary cataract model in which lens opacity appears spontaneously in the nuclear and perinuclear portions at 11-12 weeks of age. We found incidentally that the oral administration of aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase (iNOS), strongly inhibits the development of lens opacification in SCR. Since our previous results strongly suggested that calpain-mediated proteolysis contributes to lens opacification during cataract formation in SCR, we examined the calpain-mediated proteolysis in AG-treated SCR lenses in detail. The results show that the calpain-mediated limited proteolysis of crystallins is also inhibited by AG-treatment. However, the administration of AG has no effect on the substrate susceptibility to calpain. On the other hand, the autolytic activation of calpain in AG-treated lenses is strongly inhibited, although AG itself does not inhibit calpain activity in vitro. Then, we analyzed the effect of AG-treatment on calcium concentrations in lens, and found that the elevation in calcium concentration that should occur prior to cataractogenesis in lenses is strongly suppressed by AG-treatment. These results strengthen our previous conclusion that calpain-mediated proteolysis plays a critical role in the development of lens opacification in SCR. Moreover, our results indicate that the inhibition of calpain-mediated proteolysis by AG-treatment is due to the suppression of calcium ion influx into the lens cells.
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PMID:Aminoguanidine-treatment results in the inhibition of lens opacification and calpain-mediated proteolysis in Shumiya cataract rats (SCR). 1105 89

The UPL rat is a newly developed hereditary cataract model. We previously found that the administration of disulfiram, a dimer of diethyldithiocarbamate that possesses antioxidant activity, and aminoguanidine, which is known to inhibit inducible nitric oxide synthase, inhibits cataract development in selenite-induced cataract rats. In this study, we investigated the anti-cataract effects and mechanism of disulfiram and aminoguanidine on UPL rats. The opacities of UPL rat lenses, as documented by the anterior eye segment analysis system, EAS-1000 (Nidek, Aichi, Japan), increased from 39 days, and apparently mature cataracts were observed at 53 days. Accompanied with the increase in lens opacity, glutathione concentrations in UPL rat lenses decreased. The Na(+) to K(+) and water-insoluble to water-soluble protein ratios, as well as the Ca(2+) contents in UPL rat lenses increased with the development of cataracts. Oral administration of disulfiram and aminoguanidine delayed the lens opacification as well as the changes in glutathione, Na(+) to K(+) ratio, water-insoluble to soluble protein ratio, and Ca(2+) content in UPL rat lenses. The opacity and Ca(2+) content of UPL rat lenses were closely associated. The present study demonstrates that disulfiram and aminoguanidine have potency of the delay of cataract development in UPL rats, probably caused by inhibiting the rise in Ca(2+) levels.
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PMID:Delay of cataract development in hereditary cataract UPL rats by disulfiram and aminoguanidine. 1256 4

Our purpose was to study the formulation and anti-cataract effects of aqueous eye drops containing a high concentration of zinc diethyldithiocarbamate (Zn-DDC). A possible mechanism of the anti-cataract effect of Zn-DDC was also studied. Zn-DDC and hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion complex (Zn-DDC/HPbetaCD) was studied using the saturation solution method and characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (IR). Suitable formulations for Zn-DDC eye drops were established by means of in-vitro trans-corneal penetration experiments. The anti-cataract effect of the selected formulation was demonstrated by the delay in lens opacity development in hereditary shumuya cataract rats (SCRs). Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to study the effect of diethyldithiocarbamate (DDC), a metabolite of Zn-DDC, on the transcription inducible nitric oxide synthase (iNOS) mRNA in human lens epithelial cells (HLEC). In the presence of 22% (w/v) HPbetaCD, the solubility of Zn-DDC in water (0.2 mM) was increased almost 850 fold (to 17 mM), by the formation of Zn-DDC/HPbetaCD. The stoichiometry of Zn-DDC inclusion was 1:1. The Zn-DDC/HPbetaCD stability constant, Ks (1:1) was estimated to be 3453 M(-1). The ophthalmic preparation containing 0.1% HPMC and 0.1% poloxamer 188 (P188) exhibited better permeability than the others in-vitro, and significantly delayed cataract formation in SCRs compared with non-treated SCRs. DDC inhibits the transcription of iNOS mRNA in HLEC. We concluded that this drug delivery system increases both the drug solubility in aqueous eye drops and the permeability of drug through the rabbit cornea, by the formation of a drug-cyclodextrin inclusion complex and the addition of polymers and penetration enhancers. The preparation effectively prevented the development of cataracts in SCRs. DDC, the metabolite of Zn-DDC, may be one of the factors in the prevention of cataract formation because it inhibits the transcription of iNOS mRNA.
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PMID:An ocular drug delivery system containing zinc diethyldithiocarbamate and HPbetaCD inclusion complex--corneal permeability, anti-cataract effects and mechanism studies. 1548 39

We previously found that Ca2+ concentrations, inducible nitric oxide synthase (iNOS) mRNA, and protein expression in lenses of the Shumiya cataract rat (SCR) increase with the development of cataracts. In this study, we investigated the change in Ca2+-ATPase activities and ATP levels in the human lens epithelial cell line SRA 01/04 (HLE cells) with the stimulation of interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). Expression levels of iNOS mRNA in HLE cells, which were determined using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR methods, increased during stimulation with IFN-gamma (1000 IU) and LPS (100 ng/ml). NO release from HLE cells, expressed as the sum of NO2- and NO3- levels, increased with the increase in iNOS expression levels. Ca2+-ATPase activities increased and ATP levels decreased in HLE cells stimulated with the combination of IFN-gamma and LPS. Furthermore, both diethyldithiocarbamate and aminoguanidine attenuated the increase in Ca2+-ATPase activities and the decrease in ATP levels. These results suggest that excessive production of NO may cause mitochondrial damage, resulting in an increased Ca2+ concentration in the lens. The increase in Ca2+ concentration in the lens may increase Ca2+-ATPase activities.
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PMID:Inhibitors of inducible nitric oxide synthase prevent damage to human lens epithelial cells induced by interferon-gamma and lipopolysaccharide. 1701 54

The present study was designed to observe if puerarin decreases lens epithelium cell (LEC) apoptosis induced partly by peroxynitrite (ONOO(-)). One hundred and eight rats were randomly divided into control group (n=36), streptozotocin (STZ) group (n=36) and STZ + puerarin group (n=36). The rats in the control group intraperitoneally (i.p.) received 0.5 ml of saline. The rats in STZ group and STZ + puerarin group received intraperitoneal injection of STZ (45 mg/kg). Three days later, the rats in STZ + puerarin group were given puerarin (140 mg/kg per day, i.p.). On days 20, 40 and 60 of the experiment, morphologic changes of lenses were observed with slit lamp. Then the animals were sacrificed for further analysis. The amount and percentage of apoptotic LECs were determined by flow cytometry. Nitrotyrosine (NT, the foot print of ONOO(-)) was examined by immunohistochemistry. Apoptosis-related genes (iNOS, etc.) were analyzed by gene array. The results showed that in the control group, all the lenses were clear. In STZ group, gradually severe opacity of the lens was observed on days 20, 40 and 60. But in STZ + puerarin group, mild opacity of the lens was observed on day 20 and more severe on day 40, but markedly decreased on day 60. In the control group, mild apoptosis of LECs was observed. In STZ group, time-dependent increase in apoptosis of LECs was observed. In STZ + puerarin group, mild apoptosis of LECs was observed on day 20, significantly increased on day 40, but markedly decreased on day 60. There was no expression of NT in the lens in the control group, but an increased expression of NT in STZ group. In STZ + puerarin group, mild expression of NT was observed on day 20, significantly increased on day 40, but markedly decreased on day 60. There was no expression of iNOS in the lens in the control group, but continuous up-regulation of iNOS expression in STZ group. In STZ + puerarin group, mild expression of iNOS was observed on day 20, significantly increased on day 40, but markedly decreased on day 60. Except the changes of iNOS related to NO production, the other apoptosis-related genes, including BCL-2 and SOD were down-regulated, while NF-kappaB and TNFR1-FADD-caspase signal transduction way were up-regulated in STZ group. The results were opposite in STZ + puerarin group and the control group. These findings show that NT is expressed in diabetic rat lens, which proves that LEC apoptosis in diabetic lens is partly induced by ONOO(-) which may be a new oxidative damage way to form cataract. Puerarin partly decreases LEC apoptosis induced by ONOO(-) and is a potential medicine for therapy of diabetic cataract. The mechanism of puerarin dealing with diabetic cataract may be related to its direct inhibition of LEC apoptosis and antagonism of ONOO(-) in diabetic rats.
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PMID:Puerarin decreases lens epithelium cell apoptosis induced partly by peroxynitrite in diabetic rats. 1717 94

Cataractous lenses have an altered distribution of the intracellular ionic environment, and the lens ionic imbalance with increased levels of calcium (Ca2+) and sodium (Na+), coupled with decreased levels of magnesium (Mg2+) and potassium (K+), is related to cataract development in human senile cataracts. We previously found that the decrease of ATP in lenses caused lens ionic imbalance, and probably decrease in ATPase function. In this study, we investigated the effect of Mg2+ deficiency on cataract progression using human lens epithelial (HLE) cells. Expression levels of inducible nitric oxide synthase (iNOS) mRNA in HLE cells were significantly greater in Mg2+-deficient medium (Mg2+ 0.021 mM) than in normal Mg2+ medium (Mg2+ 0.77 mM). The NO release from the HLE cells cultured with Mg2+-deficient medium also increased. On the other hand, the ATP levels in HLE cells 24 h after incubation with Mg2+-deficient medium were lower than that with normal Mg2+ medium. The Ca2+- and Na+/K+-ATPase activities in HLE cells until 24 h incubation with normal Mg2+ or Mg2+-deficient medium did not change. Both diethyldithiocarbamate 10 microM and aminoguanidine 250 microM attenuated the increase of NO release, and caused an increase in ATP levels in HLE cells 24 h after incubation with Mg2+-deficient medium. These results suggest that Mg2+ deficiency enhances NO production via iNOS in the lens. It is possible that the excessive production of NO cause the decrease of ATP levels. These results show that Mg2+ deficiency in the lens may cause an acceleration of the progression of lens opacification.
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PMID:Effect of magnesium deficiency on intracellular ATP levels in human lens epithelial cells. 1720 50

We previously found that the increases in Ca2+ content in the lenses of three hereditary cataract model rats, UPL rat (UPLR), Shumiya cataract rat (SCR) and Ihara cataract rat (ICR), are inhibited by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, and that the mechanisms of Ca2+ enhancement in these rat models differ. In this study, we compare the mechanisms for dysfunction in Ca2+ regulation in UPLR, SCR and ICR. Decreases in the activity of Ca2+-ATPase were found in the lenses of SCR and ICR concurrent with cataract development. In contrast, the Ca2+-ATPase activity in UPLR with opaque lenses was higher than in those with transparent lenses. On the other hand, ATP levels were markedly decreased in UPLR with opaque lenses. The expression of cytochrome c oxidase (CCO)-1 mRNA and CCO activity in UPLR lenses was found to decrease during cataract development. The nitric oxide (NO) and lipid peroxide levels were also increased in the lenses of UPLR, SCR and ICR with opaque lenses. In UPLR, excessive NO may cause damage to the mitochondrial genome, resulting in a decrease in ATP production and increase in Ca2+-ATPase activity. The decrease in ATP content may cause the decrease in Ca2+-ATPase function resulting in the elevation in lens Ca2+. In SCR and ICR, excessive NO may cause an enhancement of lipid peroxidation resulting in the oxidative inhibition of Ca2+-ATPase. The decrease in Ca2+-ATPase activity may cause the elevation in the level of lens Ca2+, thus leading to lens opacification. Our findings show that the Ca2+ contents in the cataractous lenses of all three model rats are increased, the mechanisms for this Ca2+ enhancement is different in each rat model.
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PMID:Comparison of the mechanisms of cataract development involving differences in Ca2+ regulation in lenses among three hereditary cataract model rats. 1898 61

The aim of this study was to investigate whether curcumin and aminoguanidine (AG) prevent selenium-induced cataractogenesis in vitro. On postpartum day 8, transparent isolated lens were incubated in 24 well plates containing Dulbecco's Modified Eagle Medium (DMEM). Isolated lens of group I were incubated with DMEM medium alone. Group II: lenses incubated in DMEM containing 100microM sodium selenite; group III: lenses incubated in DMEM containing 100microM sodium selenite and 100microM curcumin; group IV: lenses incubated in DMEM containing 100microM sodium selenite and 200microM curcumin; group V: lenses incubated in DMEM containing 100microM sodium selenite and 100microM AG; group V: lenses incubated in DMEM containing 100microM sodium selenite and 200microM AG. On day 12, cataract development was graded using an inverted microscope and the lenses were analyzed for enzymic as well as non-enzymic antioxidants, lipid peroxidation (LPO), nitric oxide (NO), superoxide anion (O(2)(-)) and hydroxyl radical generation (OH) and inducible nitric oxide synthase (iNOS) activity by Western blotting and RT-PCR. All control lenses in group I were clear (0). In groups II and III, all isolated lenses developed cataract with variation in levels (+++ or ++), whereas isolated lenses from groups IV, V and VI were clear (0). In agreement to this, a decrease in antioxidants and increased free radical generation and also iNOS expression were observed in selenium exposed lenses when compared to other groups. AG (100microM) was found to be more effective in anti-cataractogenic effect than curcumin (200microM). Curcumin and AG suppressed selenium-induced oxidative stress and cataract formation in isolated lens from Wistar rat pups, possibly by inhibiting depletion of enzymic as well as non-enzymic antioxidants, and preventing uncontrolled generation of free radicals and also by inhibiting iNOS expression. Our results implicate a major role for curcumin and AG in preventing cataractogenesis in selenite-exposed lenses, wherein AG was found to be more potent.
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PMID:Anti-cataractogenic effect of curcumin and aminoguanidine against selenium-induced oxidative stress in the eye lens of Wistar rat pups: An in vitro study using isolated lens. 1948 Oct 68

The generation of free radicals has been implicated in the causation of cataract, and compounds that can scavenge free radicals ameliorate the disease process. This study investigated the possible free radical scavenging potential of curcumin at a dose of 75 mg/kg body wt on selenium-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 micromol/kg body wt) into 8- to 10-day-old rat pups led to severe oxidative stress in the eye lens as evidenced by increased nitric oxide, superoxide anion, and hydroxyl radical generation and inducible nitric oxide synthase expression that probably led to cataract formation. Selenium exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca(2+) ATPase but not Na(+)/K(+) ATPase or Mg(2+) ATPase. On the other hand, pretreatment with curcumin, but not simultaneous or posttreatment, led to a decrease in oxidative stress and also rescued the selenium-mediated increase in lens Ca(2+) and inhibition of Ca(2+) ATPase activity in the eye lens. The results of this study demonstrate that an increase in free radical generation triggered by selenium could cause inactivation of lens Ca(2+) ATPase leading to Ca(2+) accumulation. This enhanced Ca(2+) can cause activation of calpain-mediated proteolysis in the lens, resulting in lens opacification. Curcumin in this study was able to prevent selenium-induced oxidative stress leading to activation of Ca(2+) ATPase and inhibition of lens opacification. Thus, curcumin has the potential to function as an anticataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca(2+) in the eye lens.
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PMID:Curcumin prevents free radical-mediated cataractogenesis through modulations in lens calcium. 1993 68

Glycemic-induced stress is a major culprit contributing to oxidative insult that has far-reaching effects in diabetic cataract worldwide. In an attempt to prevent/delay cataract, many therapeutic agents have been identified, and among these, natural dietary sources have gained pharmacological significance. Hence, we investigated the efficacy of the methanolic garlic extract against diabetic cataract in Wistar rats. Methanolic garlic extract scavenged the transition metal ion-generated H(2)O(2) with an IC(50) of 768.8 +/- 1.76 mug/ml, showing its potential ability as an antioxidant. We have noticed lenticular opacity and oxidative damage in streptozotocin (STZ)-induced hyperglycemic rats. This is evident by the elevation of Ca(2+), Cu(2+), Na(+), Mg(2+), thiobarbituric acid reacting substances (TBARS), and carbonyl content and increased activities of polyol enzymes, glutathione peroxidase (GPx), superoxide dismutase (SOD), and up regulation of iNOS transcript and protein aggregation/cross-linking followed by a decrease in reduced glutathione (GSH), K(+) content, and tryptophan fluorescence in the cataractous lenses of STZ-induced diabetic rats. Garlic administration in a dose-dependent manner attenuated the glycemia-mediated oxidative stress as all the parameters have been found normalized more or less to that of control rats and thus delaying the progression of the lens opacity. We conclude that garlic extract has hypoglycemic and anti oxidant properties that can delay the progression of cataract as revealed in this study.
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PMID:Effect of methanolic extract of Allium sativum (AS) in delaying cataract in STZ-induced diabetic rats. 2007 34

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