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)

I have discussed five aspects of lens metabolism and their possible relationship to cataract in man, and this has left me with five fundamental questions to be answered. 1. Are the fluorescent tryptophan derivatives, found only in the lens of man and higher primates, involved in the development of brown nuclear cataract? 2. Is naphthalene cataract in rabbits a model for any type of cataract in man--i.e., are quinones ever formed in the human eye? 3. Is diabetes the only cataract in which osmotic swelling is important? 4. Does self-digestion of protein in the human lens contribute to cataract development? 5. Are the consequences of the abnormal maturation of lens fibers, which occurs in tryptophan deficiency cataract in rats, ever seen in man?
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PMID:Experimental studies on cataract. 96 16

Lens opacities in old patients are usually classified as "senile cataracts". Since there are very distinct morphologic types of opacities it is evident that we have to deal with different types of triggers in discussing the cataractogenesis. A great variety of risk factors might act as triggers for the development of opacities in aged people, and there is no doubt that among them age changes of lens metabolism are the most important. These age induced changes of lens metabolism do not only influence the energy level of lens metabolism (energy concept of lens transparency), the trigger may as well be located within the protein synthesizing system or the processes responsible for maintaining normal protein conformation, further, an exogenous intoxication may also occur. Lack of normal human lenses of all ages suited for metabolic research and an undefined classification for instance, coloration of the cataractous lens) makes biochemical research with respect to the pathogenesis of senile cataracts almost impossible. Animal models (naphthalene cataract, tryptophane-deficiency, X-irradiation) suited for the purpose may well support the basic research of this subject, even if we have to assume certain species differences of lens metabolism.
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PMID:[Aging of the lens and cataract (author's transl)]. 97 41

The naphthalene-induced cataract in rats has been studied for many years as a possible model of human aging-related cataract. While the molecular mechanism of this cataract is unclear, it has recently been demonstrated that the aldose reductase inhibitor ALO1576 can prevent lens opacification in this system. The present study was undertaken to investigate the molecular basis for the effects of naphthalene on the lens and the role of pigmentation in the cataractogenic mechanism. Cataracts were induced in five strains of rats (two pigmented, three albino) by oral administration of naphthalene. Initial lens changes were observed after 1 week by slit-lamp; by 3 weeks a distinct shell-like opacity was present in the deep cortex. Little difference in the course of opacification was found between the pigmented and albino strains. Major biochemical effects were a decrease of 20-30% in glutathione (GSH) by 1 week of feeding, disulfide cross-linking of lens proteins present by 3 weeks, and a nearly 20-fold increase in the content of protein-GSH mixed disulfide. No effect was seen in the ability of the affected lenses to accumulate activity [3H]choline or 86Rb from the medium in organ culture nor in the activity of the Na+/K(+)-ATPase. ALO1576 (10 mg kg-1 day-1) completely prevented all morphological and biochemical changes in the lenses of the naphthalene-fed rats in both pigmented and non-pigmented strains. These results indicate that pigmentation is not required for induction of naphthalene cataract in rats. Naphthalene dihydrodiol was found in the aqueous humor and lens of naphthalene-fed rats. It is proposed that naphthalene dihydrodiol produced in the liver reaches the aqueous humor and penetrates the lens where it is further metabolized ultimately to form the toxic species, naphthoquinone.
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PMID:The possible mechanism of naphthalene cataract in rat and its prevention by an aldose reductase inhibitor (ALO1576). 154 42

In the past, almost all studies on naphthalene cataract were based on in vivo experiments. Such studies are laborious and time-consuming and are complicated by systemic toxicity arising from the metabolites of naphthalene. In order to study the direct effects of naphthalene metabolites on the lens, we established an in vitro 'naphthalene cataract' model system by exposing rat lens to naphthalene dihydrodiol (2.5 x 10(5) M) containing medium for 48 hr. Under these conditions, we analysed several biochemical parameters including the glutathione level, protein mixed disulfides, protein patterns on SDS-gels, active transport, NA+/K(+)-ATPase activities and the measurement of naphthalene metabolites in the cultured lenses. The results showed that both the morphological and biochemical changes were very similar to those observed in lenses of rats fed naphthalene (1 g kg-1 day-1). Furthermore, ALO1576 completely blocked the in vitro changes as it did in vivo. Therefore, this model system can be used as a new tool to investigate the mechanism of naphthalene cataract formation. Other naphthalene metabolites such as 1-naphthol, 2-naphthol, 1,2-dihydroxynaphthalene and 1,2-naphthoquinone were also studied in vitro and the results showed that the effects of these naphthalene metabolites were very different from those observed in naphthalene cataracts in vivo.
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PMID:Establishment of a naphthalene cataract model in vitro. 154 43

The topographic distribution of enzyme activities in normal rat lenses and their changes occurring during naphthalene cataract development were investigated. Cataract formation was documented by slit images according to the Scheimpflug principle. Before the onset of visible changes and after the development of early visible opacities, the animals were sacrificed, their lenses removed and biochemically analyzed. The lenses were divided reproducibly into 6 parts--the equatorial ring and 5 layers of central cylinders from the anterior to the posterior cortex. The enzyme activity spectra (AR, SDH, GR, GPX, PFK, ALD, GAP-DH, and LDH) showed region-related patterns, which could not be detected with analysis of the total lens. Image analysis of the first signs of opacity showed that changes in the activities of several enzymes correlate with density changes in the corresponding lens layers.
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PMID:Enzymatic distribution patterns of rat lenses and the changes that occur during naphthalene cataract development. 160

This investigation compared the effects of two types of aldose reductase inhibitors on several biochemical parameters in naphthalene-induced cataract of the rat over a time span of 102 days of treatment. Feeding of naphthalene daily to brown Norway rats resulted in gradual, progressive development of zonular opacities. As compared to control animals, the values of soluble protein, soluble glutathione (total of oxidized plus reduced) and activities of glutathione peroxidase and glutathione reductase were decreased in rats fed either naphthalene or naphthalene + FK366, a carboxylic-acid-type aldose reductase inhibitor. In marked contrast, treatment with A11576, a hydantoin-type aldose reductase inhibitor, maintained the values of most parameters (with one exception) at levels that were similar to those of the controls, and all lenses remained clear. A decline of glutathione was noted in all naphthalene-fed rats, irrespective of whether these animals had been treated with an aldose reductase inhibitor. The great decrease of glutathione with A11576 suggests that this inhibitor acts at some step in naphthalene metabolism following formation of naphthalene epoxide.
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PMID:Naphthalene-induced cataract in the rat. II. Contrasting effects of two aldose reductase inhibitors on glutathione and glutathione redox enzymes. 178 59

Conditions of oxidative stress may lead to cataract formation. Reaction of certain flavoproteins, the NADH: oxidoreductases, with different quinones is well known to form hydrogen-peroxide. This reaction was investigated to get more information on cataract induction by naphthalene and its quinone metabolites. Protein extracts from bovine lens cortex exhibit "diaphorase" activity, indicated as dye reduction in the presence of NADH and dichlorophenol-indophenol (DCPIP) or ferricyanide. Different redox cycling compounds are shown to be active in this "diaphorase" reaction by lens protein extract (LCE): Oxygen consumption can be detected in the presence of pyrroloquinoline quinone and juglone whereas 1,4-naphthoquinone, menadione and paraquat are no redox cyclists in this flavoprotein catalyzed reaction.
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PMID:Cataract induction by 1,2-naphthoquinone. I. Studies on the redox properties of bovine lens proteins. 187 11

Naphthalene cataract is probably due to peroxide production through naphthoquinone (NQ) redox cycling and/or glutathione conjugation. Both mechanisms yield losses of essential SH-groups in cristallins and are thus probably involved in protein modification finally visible as lens opacity. 1,2-Naphthoquinone produces H2O2 in the presence of either ascorbate, glutathione, NADH or--to a lesser extend--by homogenates of lens protein preparations. In the presence of 1,2-naphthoquinone and the above reductive additions, both, oxygen uptake and H2O2 formation can be observed. Reductive oxygen activation in these systems are diminuated by iodide in a concentration-dependent manner. Since maleimide-treated proteins are less capable to activate oxygen by 1,2-naphthoquinone, a direct oxygen activation by the interactions of 1,2-naphthoquinone with protein-SH is indicated. Catalysis of "diaphorase"-type (dia) enzymes via NADH--dia--1,2-NQ--O2 seems not to operate in hydrogenperoxide production during 1,2-naphthoquinone lens toxicity.
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PMID:Cataract induction by 1,2-naphthoquinone. II. Mechanism of hydrogenperoxide formation and inhibition by iodide. 187 12

Naphthalene feeding can result in cataract formation in rats and rabbits due to specific metabolites of naphthalene. The concomitant administration of the aldose reductase inhibitor Al1576 to naphthalene-fed rats was proven to prevent cataract formation. To determine whether this effect was directly linked to the ability of Al1576 to inhibit enzyme aldose reductase, a variety of structurally diverse aldose reductase inhibitors, including the carboxylic acids tolrestat, Ponalrestat, and FK366, and the spirohydantoins, sorbinil and Al1576, were investigated for their ability to inhibit naphthalene-induced cataracts. Brown Norway rats, administered naphthalene by gavage, were fed normal rat chow containing these aldose reductase inhibitors at levels known to inhibit sugar cataract formation. The lens changes in these rats were monitored over a 90-day period by portable slit-lamp microscopy and histologic study. Al1576 showed a dose-dependent reduction in naphthalene-induced cataract formation, with no naphthalene-associated deposits seen in toluidine blue-stained lens sections. Sorbinil also reduced lens changes, whereas tolrestat, Ponalrestat, and FK366 had no effect. These results suggest that inhibition of naphthalene-induced cataract formation by structurally diverse aldose reductase inhibitors was not linked to the inhibition of aldose reductase.
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PMID:Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat. 190 36

The naphthalene cataract in the pigmented rabbit, in contrast to the corresponding model in the pigmented rat, is characterized by a rather unstable cataract development during the later stages. Some animals rapidly develop mature cataracts, others develop cortical cataracts with almost no further progression inspite of a continued naphthalene treatment. To get more insight into this phenomenon, a study with pigmented rabbits (8 weeks old) was designed and at different stages of cataract development lenses were separated in single layers with the Bonn freeze-sectioning device. The key enzymes of the carbohydrate metabolism and the redox potential were determined in those layers. The results of the biochemistry failed however to explain the prominent differences of cataract development in-vivo. We conclude from these findings that the naphthalene cataract model in the pigmented rabbit shall no longer be used in drug side-effect or efficacy studies.
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PMID:Regional enzyme profiles in rabbit lenses with early stages of naphthalene cataract. 195 37


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