UMLS:C0086543 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

The focus of the study was to characterize plasma membrane calcium-ATPase pump (PMCA) isoform expression in the human lens and cultured lens epithelial cells as a basis for future studies of calcium homeostasis in the lens. Proteins and mRNA expression were analysed using Western Immunoblotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. Clear human lenses from the Kentucky Lions Eye Bank and an immortalized human lens epithelial cell line (HLE B-3) were used. RT-PCR products of PMCA1, PMCA2, and PMCA4 primers were detected at 429, 557, and 849bp, respectively. All these products were identified as PMCA isoforms by sequence analysis. Protein bands at approximately 130, 115, and 135kDa were detected by Western blot analysis for PMCA1, PMCA2 and PMCA4, respectively. PMCA3 was not detected at protein or mRNA level in any human lens sample or cell culture, but was detected in the rat brain cortex used as a control. Several bands with lower molecular weights, especially for PMCA2, were detected in the epithelial samples and probably represent break down products of PMCA2. No PMCA proteins or breakdown products were detected in the nuclear or cortical fractions from human lenses. PMCA1, 2, and 4 proteins and mRNAs are expressed in human lens epithelium and cultured epithelial cells; PMCA3 is not. PMCA was not detected at all in the lens fibre cells. The calcium pump must be selectively processed, independent of other membrane proteins such as the Na-K-ATPase pumps, because the distribution of the Na-K-ATPase pump is asymmetrical in the epithelium and present throughout the lens whereas the calcium pumps are not. The findings of this study provide a basis for further studies to examine the role and modulation of PMCA isoforms in calcium homeostasis and in the development of cataract.
...
PMID:Plasma membrane Ca2+-ATPase expression in the human lens. 1597 55

It is well known that the incidence of cataract is higher in diabetics as compared to non-diabetics. Its rate of maturation is also faster in the diabetics. The precise mechanism of this acceleration is not clearly understood. It is hypothesized that this could be a result of the combination of the metabolic and oxidative stress induced by glycemia itself with the age-associated increase in ambient generation of oxyradical species. In the current studies, we have investigated this possibility using the galactose cataract model. Galactosemia was induced by feeding rats a 50% galactose diet. The increased susceptibility of the glycemic lenses to physiological damage by reactive oxygen species (ROS) was studied by incubating them in Tyrode in the absence and presence of menadione. The resulting physiological damage to the lens was assessed initially in terms of its ability to maintain Na+-K+ ATPase dependent active transport of potassium ions, as represented by the uptake of rubidium ions. Subsequently, the level of ATP, indexing the general metabolic status, and the level of glutathione (GSH), indexing the status of antioxidant reserve, were also determined. The uptake of rubidium in the normal lenses incubated in the presence of the quinone was depressed to more than 50% of the controls run in the basal medium. A similar depression existed in the galactosemic lenses in comparison to the normal lenses. However, in the presence of menadione, the inhibition of the uptake was accentuated further in the case of galactosemic lenses, the uptake here being only 20% of the normal controls. Similarly, the galactosemic lenses were also more susceptible to menadione dependent decrease in ATP and GSH.
...
PMID:Combination of glycemic and oxidative stress in lens: implications in augmentation of cataract formation in diabetes. 1603 27

Phospholipase D (PLD), a highly regulated enzyme that generates the second messenger phosphatidic acid, functions in signal transduction, membrane trafficking and cytoskeletal reorganization. PLD is thought to be involved in the pathogenesis of diabetic complications by activating PKC. Since PKC and PLD are present in the lens we sought to determine if PLD plays a role in diabetic cataract development. We developed transgenic mice that overexpress PLD2, one of the two mammalian isoforms of PLD. These mice developed congenital nuclear cataracts, but not diabetic cataracts. Histological analysis revealed vacuole formation in the fiber cells, mediated potentially by the substantially increased Na,K-ATPase activity. In the presence of the aldose reductase overexpressing transgene that increases lens osmotic pressure, these double transgenic mice developed more severe congenital cataract and became susceptible to develop diabetic cataract. Together, these data suggest that increased PLD2 activity in the lens under hyperglycemic condition might impair its osmoregulatory mechanism and reduce its ability to cope with the osmotic stress triggered by sorbitol accumulation.
...
PMID:Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract formation through modulation of Na,K-ATPase activity and osmotic stress. 1679 33

Our purpose was to investigate the effects of exposure to high partial pressure of oxygen on lens optical quality and on the activities of lenticular catalase and Na, K-ATPase in culture and to examine the effect of zinc-desferrioxamine (Zn-DFO) addition to cultured lenses exposed to high oxygen partial pressure on these parameters. Bovine lenses, kept in organ culture, were exposed to different combinations of partial pressure of oxygen with and without addition of Zn-DFO complex (20 microM) and examined during a 14-day period. Lens optical quality, catalase, and Na, K-ATPase activity were compared between study and control groups. Two hundred lenses were included in the present study. Decreased lenticular optical quality and decreased catalase and Na, K-ATPase activities were observed in lenses exposed to hyperbaric oxygen. Lenses exposed to normobaric oxygen showed a reduction in these parameters to a lesser degree. The damaging optical and enzymatic effects of oxygen on lenses in culture increased in magnitude along the culture period. Addition of Zn-DFO to the culture just before the exposure to hyperbaric oxygen eliminated most of the optical and enzymatic oxygen-induced damage. Addition of Zn-DFO after the first exposure demonstrated reduction in the oxidative damage induced reduction of optical quality in a time-dependent manner - the later the addition of Zn-DFO took place the smaller the protective effect observed. High oxygen load has toxic effects on bovine lenses in organ culture conditions as determined by optical parameters as well as reduction of catalase and Na, K-ATPase activities. These toxic effects can be attenuated by introducing Zn-DFO just before lenses are exposed to oxygen. The beneficial effect of Zn-DFO, applied after lenses have been exposed to hyperbaric oxygen, on the oxidative damage was time-dependent - the earlier the application the more significant the observed protective effect. The present results may indicate a possible future role for Zn-DFO as a protective agent against oxygen-induced human cataract formation.
...
PMID:Zinc-desferrioxamine reduces damage to lenses exposed to hyperbaric oxygen and has an ameliorative effect on catalase and Na, K-ATPase activities. 1717 2

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.
...
PMID:Effect of magnesium deficiency on intracellular ATP levels in human lens epithelial cells. 1720 50

The UPL rat is a newly developed hereditary cataract model. We previously found that the ATP content in UPL rat lenses decreases during cataract development, and the decrease in ATP content causes Ca(2+)-ATPase dysfunction resulting in an elevation in Ca(2+) and cataract development. In addition, we reported that the oral administration of disulfiram and aminoguanidine ameliorates the decrease in ATP content and the elevation in Ca(2+) content in UPL rat lenses. In this study, we demonstrate the effect of nitric oxide (NO) on the expression and activity of cytochrome c oxidase (CCO) in normal and UPL rat lenses during cataract development. We also determined the effects of the oral administration of disulfiram and aminoguanidine on the mRNA expression and activity of CCO and NO production in UPL rat lenses. The expression of CCO-1 mRNA in UPL rat lenses, determined by a quantitative real-time RT-PCR method, decreased during cataract development. CCO activity in UPL rat lenses also decreased with aging. On the other hand, the oral administration of disulfiram and aminoguanidine attenuated the decrease in CCO-1 mRNA expression and CCO activity. These results suggest that excessive NO causes the decrease in CCO-1 mRNA expression and CCO activity, and that the decrease in CCO may cause the decrease in ATP production in UPL rat lenses. Disulfiram and aminoguanidine may attenuate the decrease in ATP production, resulting in a delay in cataract development.
...
PMID:Adverse effects of excessive nitric oxide on cytochrome c oxidase in lenses of hereditary cataract UPL rats. 1793 68

Our previous studies have demonstrated that the instillation of eye drops containing disulfiram, a radical scavenger and nitric oxide synthase inhibitor, delays cataract development in ICR/f rats, and we have suggested that the production of nitric oxide (NO) and lipid peroxide (LPO) in the lens may relate to the delay in cataract development brought about by disulfiram. However, the involvement of NO and LPO in lenses of ICR/f rats during cataract development has not yet been established. In the present study, we determined changes in NO and LPO levels in lenses of ICR/f rats during cataract development. Opacification of ICR/f rat lenses started at 77 days of age, and the lenses of 91-day-old ICR/f rats were almost entirely opaque. The Ca(2+)-ATPase activity in the lenses of ICR/f rats decreased with increasing age, and an elevation in Ca(2+) content was observed in ICR/f rat lenses with the decrease in Ca(2+)-ATPase activity. NO levels in the lenses of ICR/f rats increased from 63 to 85 days of age, reaching a maximum at 77 days of age. In addition, LPO levels in the lenses of ICR/f rats also increased with increasing age. LPO levels in the lenses of 63- to 91-day-old ICR/f rats were found to be significantly higher compared with those in 22-day-old ICR/f rats. These changes of Ca(2+), Ca(2+)-ATPase, NO and LPO were attenuated by instillation of DSF eye drops. These results suggest that excessive NO may cause enhanced lipid peroxidation resulting in the inhibition of Ca(2+)-ATPase. The decrease in Ca(2+)-ATPase activity may cause the elevation in lens Ca(2+), leading to lens opacification in ICR/f rats.
...
PMID:Inhibitive effects of enhanced lipid peroxidation on Ca(2+)-ATPase in lenses of hereditary cataract ICR/f rats. 1840 84

Diabetes is a major contributing factor in cataract development. In animal models where cataracts develop within days or weeks of diabetes it is well established that osmotic stress from the accumulation of sorbitol leads to cataract development. This mechanism might explain the rare cases of acute cataract sometimes found in patients with uncontrolled sustained hyperglycemia but cannot account for the vast majority of cataracts that developed after years of diabetes. Thus, a model that can simulate diabetic slow-developing cataract is needed. The contribution of osmotic and oxidative stress in cataract development in sorbitol dehydrogenase (SDH) deficient mice, a model for slow-developing cataract in diabetic patients was determined. Contribution of osmotic stress was assessed by HPLC measurement of sorbitol and by observing the effect of blocking sorbitol accumulation by aldose reductase (AR) null mutation in the SDH deficient mice. Contribution of oxidative stress was assessed by observing the effect of vitamin E treatment and the effect of null mutation of glutathione peroxidase-1 (Gpx-1) on cataract development in these mice. Lenticular sorbitol level was significantly increased in the SDH deficient mice, and blocking sorbitol accumulation by the AR null mutation prevented cataract development, demonstrating the contribution of osmotic stress in cataract development. SDH deficiency did not affect lens oxidative stress status. However, treatment with vitamin E significantly reduced the incidence of cataract, and Gpx-1 deficiency exacerbated cataract development in these mice. Our findings suggest that chronic oxidative stress impaired the osmoregulatory mechanism of the lens. This was not evident until modest increases in lens sorbitol increased the demand of its osmoregulatory function. This osmoregulatory dysfunction model is supported by the fact that the activity of Na+/K+-ATPase, the key regulator of cellular ions and water balance, was dramatically reduced in the precataractous lenses of the SDH deficient mice, and that treatment with vitamin E prevented the loss of Na+/K+-ATPase activity. This osmoregulatory dysfunction model might explain why diabetic patients who control their blood glucose moderately well are still susceptible to develop cataract.
...
PMID:Synergistic effect of osmotic and oxidative stress in slow-developing cataract formation. 1876 Feb 74

Excessive Ca(2+) can be detrimental to cells and raised levels of Ca(2+) in human lenses with cortical cataract have been found to play a major role in the opacification process. Ca(2+) homeostasis is therefore, recognised as having fundamental importance in lens pathophysiology. Furthermore, Ca(2+) plays a central role as a second messenger in cell signalling and mechanisms have evolved which give cells exquisite control over intracellular Ca(2+) ([Ca(2+)](i)) via an array of specialised regulatory and signalling proteins. In this review we discuss these mechanisms as they apply to the lens. Ca(2+) levels in human aqueous humour are approximately 1 mM and there is a large, 10,000 fold, inwardly directed gradient across the plasma membrane. In the face of such a large gradient highly efficient mechanisms are needed to maintain low [Ca(2+)](i). The Na(+)/Ca(2+) exchanger (NCX) and plasma membrane Ca(2+)-ATPase (PMCA) actively remove Ca(2+) from the cells, whereas the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) sequesters Ca(2+) in the endoplasmic reticulum (ER) Ca(2+) store. In lens epithelial cells the dominant role is played by the ATPases, whilst in the fibre cells NCX activity appears to be more important. Usually, [Ca(2+)](i) can be increased in a number of ways. Ca(2+) influx through the plasma membrane, for example, is mediated by an array of channels with evidence in the lens for the presence of voltage-operated Ca(2+) channels (VOCCs), receptor-operated Ca(2+) channels (ROCCs) and channels mediating store-operated Ca(2+) entry (SOCE). Ca(2+) signalling is initiated via activation of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTK) of which the lens expresses a surprisingly diverse array responding to various neurotransmitters, hormones, growth factors, autocoids and proteases. Downstream of plasma membrane receptors are IP(3)-gated channels (IP(3)Rs) and ryanodine receptors (RYRs) located in the ER, which when activated cause a rapid increase in [Ca(2+)](i) and these have also been identified in the lens. Through an appreciation of the diversity and complexity of the mechanisms involved in Ca(2+) homeostasis in normal lens cells we move closer to an understanding of the mechanisms which mediate pathological Ca(2+) overload as occurs in the process of cataract formation.
...
PMID:The mechanisms of calcium homeostasis and signalling in the lens. 1906 88

Recent investigations have shown that phytochemical antioxidants can scavenge free radicals and prevent various diseases. Cataract is the leading cause of blindness and is associated with oxidative damage of the lens. Selenite-induced cataract in rat pups is an excellent mimic of oxidative stress-induced cataract. Selenite cataract is associated with oxidative stress, loss of calcium homeostasis, calpain activation and protein insolubilization in the lens. Our present study focuses on the isolation of flavonoids from Vitex negundo and to assess its efficacy in preventing these changes in the lens of selenite-induced cataract models. Eight-day-old Sprague-Dawley rat pups were used for the study and divided into four groups: Control (G I), Sodium selenite-induced (G II), Sodium selenite+quercetin treated (G III), Sodium selenite+flavonoids from Vitex negundo (FVN) (G IV). Cataract was induced by a single subcutaneous injection of Sodium selenite (4 mg/Kg body weight) on the 10th day. Treatment groups received quercetin (1.0mg/Kg body weight) and FVN (1.0mg/Kg body weight) intraperitoneally from 8th to 15th day. Cataract was visualized from the 16th day. Morphological examination of the rat lenses revealed no opacification in G I and mild opacification in G III and G IV (stage 1) whereas dense opacification in G II (stage 4-6). The activities of superoxide dismutase (SOD), catalase, Ca(2+)ATPase, concentration of reduced glutathione (GSH) and protein sulfhydryl content were significantly increased in G III and G IV compared to G II, while decreased activities of calpains, lower concentration of calcium and thiobarbituric acid reactive substances (TBARS) were observed in G III and IV as compared to G II. Lens protein profile of water soluble proteins showed normal levels of expression in treated groups compared to that of selenite-induced rats. These results indicate good antioxidant and therapeutic potential of FVN in modulating biochemical parameters against selenite-induced cataract, which have been reported in this paper for the first time.
...
PMID:Vitex negundo attenuates calpain activation and cataractogenesis in selenite models. 1909 87

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>