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)

Macular edema has been observed frequently in man after cataract extraction, but pathogenic mechanisms remain unclear. Seven eyes of four young adult rhesus monkeys underwent lens extraction. The retinas and maculae of these eyes were examined by ophthalmoscopy fundus photography, fluorescein angiography, light and electron microscopy, and the horseradish peroxidase tracer technique. In the macular region, the blood-retinal barrier at the retinal vasculature was disrupted in three of the seven eyes. All three eyes had had vitreous loss during lens extraction. Horseradish peroxidase was observed both intracellularly and extracellularly in the maculae. In contrast, the blood-retinal barrier at both the retinal pigment epithelium and the retinal vasculature of the peripheral retina in most eyes was intact. We conclude that macular edema secondary to lens extraction is due to disruption of the blood-retinal barrier at the levels of the retinal vasculature and the retinal pigment epithelium.
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PMID:Experimental macular edema after lens extraction. 40 67

Lens permeability has been shown to be compromised during galactose-induced cataract development in rats. Recent studies have demonstrated permeability and diffusion pathways as well as endocytotic activity in normal lenses of different species using tracers of different molecular weights. We investigated the permeability and diffusion of tracers in normal rat lenses and in lenses during cataract development using three different molecular weight tracers, lanthanum nitrate (LN, MW 430), ruthenium red (RR, MW 858.5) and horseradish peroxidase (HRP, MW 40.000) for this study. Sprague Dawley rats weighing 50gms were fed Purina Rat Chow with or without galactose. Our results, based on transmission electron microscopy, show that all tracers penetrated through the capsule and the basal portion of the intercellular spaces. While the diffusion of RR was restricted to the epithelial cell layer, LN and HRP were observed in intercellular spaces in cortical fiber cells. In the HRP "washout" studies, HRP could be readily removed from the intercellular spaces in the basal region in the epithelial cell layer. This and other observations suggest the presence of a barrier (tight-junction) in the apical region. Our studies also suggest an influx of tracers in the lens, specifically LN and HRP, through the equatorial region. The permeability of the tracers increased and endocytotic vesicles with tracers were often found associated with the lateral and basal membranes of epithelial cells in the galactose-fed rats at the precataractous and mature cataractous stages. This study provides further support for the presence of a tight-junction between epithelial cells and indicates the movement of tracers through the equatorial region. Moreover, it confirms previous observations that indicated alterations in lens permeability during galactose cataractogenesis.
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PMID:Alterations in lens permeability during galactose cataract development in rat. 137 37

Nuclear cataract formed in rat lens in response to a protocol of multiple, low doses of sodium selenite. Nuclear cataract occurred, in both Wistar and Sprague-Dawley rats, following five subcutaneous injections of selenite over an 8-day period with an accumulated dose of 40-50 nmol selenite g-1 body weight. Glutathione content decreased within the first 24 hr of treatment and remained at 60% of controls. Lipid peroxidation occurred in Wistar rats prior to nuclear cataract formation. A two to three-fold increase in calcium concentration and decreased protein content accompanied nuclear cataract development. Enzyme activities were measured for glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and only the peroxidase activity remained constant through the period of cataract formation. This protocol resulted in nuclear cataracts similar in appearance to those observed with a single, acute dose of selenite. The opportunity to control the rate of selenite-dependent cataract formation allows further definition of precataractous events.
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PMID:Biochemical changes and cataract formation in lenses from rats receiving multiple, low doses of sodium selenite. 147 77

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

Lens antioxidative enzyme activity (catalase, superoxide dismutase, glutathione peroxidase) in cataract as well as the possibility of cataract induction by the lipid peroxidation products and their influence on the content of reduced thiols (oxy-red balance) were studied. It was shown that the rate of the H2O2 decomposition by the human cataract lenses is lowered in comparison with the normal lenses. This is not due to the lowered catalase or glutathione-peroxidase 1 activity, but depends on the deficiency of reduced glutathione in the lens. Activity of superoxide dismutase and glutathione peroxidase metabolizing organic hydroperoxides is significantly lowered in the cataract lenses. Lipid peroxidation products injected into the rabbit vitreous induce posterior subcapsular cataract, which is accompanied by depletion of reduced glutathione level in the lens. The conclusion is made that two interrelated processes: accumulation of H2O2 and of lipid peroxides induce aggregation of the soluble proteins and the fragmentation of the membrane structures in cataract lenses.
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PMID:[Antioxidative enzyme activity and metabolism of peroxide compounds in the crystalline lens during cataractogenesis]. 381 88

Lipid peroxidation (LPO) could be one of the mechanisms of cataractogenesis, initiated by enhanced production of oxygen free radicals in the eye fluids and tissues and impaired enzymatic and non-enzymatic defences of the lens. The increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides) and end fluorescent LPO products were detected in the lipid moiety of the aqueous humor samples obtained from patients with cataract as compared to normal donors. Isolated human transparent and cataractous lenses and normal mouse and rabbit lenses were incubated with liposomes in organ culture in the presence and absence of LPO inhibitors, free radical scavengers and enzymes (catalase, superoxide dismutase (SOD)) in order to examine the potential of the lenses to induce LPO in the surrounding medium. LPO assayed spectrophotometrically were diene and triene conjugates, and malonaldehydes (MDA) were determined as thiobarbituric acid-reactive material. A chemiluminescence detection catalysed by peroxidase was used to measure H2O2 and O2-. was assayed spectrophotometrically using cytochrome C reduction. The level of lipid peroxides in liposomes was significantly (2.5-4.5-fold) higher after 3 h of incubation of the transparent lenses (or the lenses at the initial stage of cataract) than after the proper time of incubation of human mature cataractous lenses and virtually no oxidation of liposomes was detected in the absence of the lens. LPO in this system was decreased in the presence of free radical scavengers and enzymes that degrade H2O2 (EDTA, SOD, L-carnosine, chelated iron and catalase). The most effective agent was EDTA which chelates the free metal cations required to generate O2-. radicals that initiate the free radical process culminating in LPO. Lenses generated more H2O2 into the medium in the presence of exogenous ascorbate. Release of the oxidants, (O2-., H2O2, OH. and lipid hydroperoxides) by the intact lenses in the absence of respiratory inhibitors indicates that these metabolites are normal physiological products inversely related to the lens life-span potential (maturity of cataract) generated, probably, through the metal-ion catalysed redox-coupled pro-oxidant activation of the lens reductants (ascorbic acid, glutathione).
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PMID:Lipid peroxide and reactive oxygen species generating systems of the crystalline lens. 831 81

Selenium (Sc) is a trace element which incorporates into the selenoenzyme glutathion peroxidase. Cataractogenesis may be caused either by the excess or deficiency of this trace element. More recently, its potential of becoming a possible environmental pollutant has been emphasized. In an attempt to reveal the relationship of this element with cataractogenesis, we detected its level in 48 serum, 36 lens and 9 aqueous humour samples of 48 patients with senile cataract, comparing the results with appropriate controls. Selenium levels (mean +/- SD) of cataractous patients were found to be 0.28 +/- 0.04 microgram/ml (CI: 0.27 to 0.29 microgram/ml) in sera (controls: 0.32 +/- 0.04 microgram/ml; CI: 0.30 to 0.34 microgram/ml, p < 0.0001), 5.43 +/- 3.07 microgram/g dry weight (CI: 4.43 to 6.43 microgram/g dry weight) in lens (controls: 4.43 +/-2.53 microgram/g dry weight; CI: 2.78 to 6.08 microgram/g dry weight; p=0.374) and 0.19 +/- 0.06 microgram/ml (CI:0.15 to 0.23 microgram/ml) in aqueous humour samples (controls: 0.31 +/-0.12 microgram/ml; CI: 0.24 to 0.38 microgram/ml, p = 0.02). When patient subgroups were analyzed, serum Se levels were found to be 0.28 +/- 0.05 microgram/ml (CI: 0.26 to 0.30 microgram/ml in the nuclear cataract and 0.28 +/- 0.02 microgram/ml (CI: 0.27 to 0.30 microgram/ml) in the cortical cataract. Lens Se levels, on the other hand, were detected as 5.91 +/- 3.56 microgram/g dry weight (CI:4.49 to 7.33 microgram/g dry weight) in the nuclear cataract and 4.47 +/- 1.40 microgram/g dry weight (CI: 3.68 to 5.26 microgram/g dry weight) in the cortical cataract. It is anticipated that decreased Se in aqueous humour and sera of patients with senile cataract may reflect defective antioxidative defense systems which may lead to the formation of cataract.
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PMID:Selenium concentrations in serum, lens and aqueous humour of patients with senile cataract. 864 78

microPx-11, a ferriheme undecapeptide proteolytic degradation product of cytochrome C is shown to be a peroxidase with broad specificity degrading H2O2 and tertiary butyl hydroperoxide. It is also capable of effectively eliminating superoxide and hydroxyl radical. The peroxidase loses activity in the presence of peroxide unless it is stabilized by ascorbate (Asc) or solutions such as aqueous humor or medium 199. While thiol but not disulfides inactivates the microPx-11, it is not inhibited in the presence of the rat lens which has a high GSH content. microPx-11 at concentrations 10 to 50 fold greater than are required to achieve good protective activity exhibits no toxicity based on cell viability, ATP levels and lens transparency after long-term incubations of alpha TN4-1 cells or cultured rat lens. The peroxidase is capable of protecting cultured rat lenses from photochemical stress where H2O2, O2.- and OH. are generated based on transparency, choline transport, epithelial cell viability and protein integrity as indicated by SDS-PAGE of the rat lens protein. In the absence of the peroxidase, extensive epithelial cell death and other degradative changes are observed. The DNA of alpha TN4-1 cells can also be protected from H2O2 induced single strand breaks by the microPx-11. The overall results suggest that a number of cytochrome C proteolytic degradation products are peroxidases which may be effective anti-cataract agents protecting the lens from oxidative stress.
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PMID:Microperoxidases catalytically degrade reactive oxygen species and may be anti-cataract agents. 946 80

Studies of the in vitro inhibitory effects of drugs most often used in the treatment of primary glaucoma on the generation of the main active oxygen forms (hydroxyl radical, superoxide anion radical, singlet oxygen and radical products of hydrogen peroxide and peroxidase reaction) showed that antiradical activity is more intrinsic for thimolol and decreases in the following series: betoptic-pilocarpinclofelin. This once more validates the efficacy of beta-blockers in the treatment of glaucoma and prevention of cataract associated with it.
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PMID:[Comparative study of antiradical effects of several antiglaucoma drugs]. 962 11

The interaction of hydrogen peroxide, ascorbate and microperoxidase-11 (MP11), a ferriheme undecapeptide derived from cytochrome c, has been investigated using spectrophotometry, oxymetry, electron paramagnetic resonance (EPR), and mass spectroscopy techniques. It is shown that in 50 m M phosphate pH 7. 0-7.4 in the absence of other reactants H(2)O(2)induces a concentration-dependent decrease in absorption at the Soret band (399 nm) of the microperoxidase, with concomitant H(2)O(2)decomposition and oxygen evolution. The reaction causes irreversible heme degradation, concomitant with loss of enzymatic activity. Ascorbate effectively protects MP11 from degradation and inhibits oxygen evolution. At ascorbate concentrations greater than that of H(2)O(2), microperoxidase degradation is almost completely prevented. Mass spectrometry showed that H(2)O(2)oxidizes the microperoxidase to a monooxygenated product, which did not form if ascorbate was included in the reaction system. There appears to be a 1:1 relationship between H(2)O(2)degradation and ascorbate oxidation. EPR experiments revealed that an ascorbate radical was formed during the reaction. These reactions may be described by a scheme where a putative 'compound I' of the microperoxidase is reduced by ascorbate back to the original redox state (ferric) of the peroxidase in two one-electron steps, concomitantly with oxidation of the ascorbate to an ascorbate radical or in one two-electron transfer step forming dehydroascorbate. In the absence of ascorbate, the 'compound I' reacts further with the peroxide causing microperoxidase degradation and partial oxygen evolution. These observations are relevant to the interaction of ferrihemes with H(2)O(2)and ascorbic acid and may be pertinent for the potential application of MP11 as an anti-cataract agent.
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PMID:Investigation of the mechanism of action of microperoxidase-11, (MP11), a potential anti-cataract agent, with hydrogen peroxide and ascorbate. 1093 Mar 23


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