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)

Research on the sugar metabolism of the crystalline lens, past and preent, is reviewed. The chief energy source in the lens is the Embden-Meyerhof pathway; respiration and oxidative phosphorylation become more important as the lens ages. The function of the alpha-glycerophosphate cycle is not fully understood. The mechanisms involved in cataract formation, including those of hypoglycemic cataract and osmotic cataracts, are discussed. Sugar cataracts can be delayed or prevented with such aldose reductase inhibitors as flavonoids. By inhibiting aldose reductase, the formation and accumulation of sugar alcohols is stopped. This approach may be useful as a medical therapy for human diabetic senile cataracts.
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PMID:Sugar metabolism in the crystalline lens. 10 Aug 92

The ocular lens, which is continually exposed to light and ambient oxygen, is at high risk of photooxidative damage resulting in cataract. Oxygen free radicals appear to impair not only lens crystallins which will aggregate and precipitate forming opacities but also proteolytic enzymes whose function it would be to eliminate the damaged proteins. Apart from an enzymatic defense system consisting of superoxide dismutase, catalase and glutathione peroxidase against excited oxygen species the lens contains the antioxidant vitamins C, E and presumably beta-carotene as another line of defense. In vitro and in vivo studies in different animal species have demonstrated a significant protective effect of vitamins C and E against light-induced cataract. Sugar and steroid cataracts were prevented as well. Epidemiological evidence in humans suggests that persons with comparatively higher intakes or blood concentrations of antioxidant vitamins are at a reduced risk of cataract development. These positive findings established by several research groups justify extensive intervention trials with antioxidant vitamins in humans using presenile cataract development as a model.
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PMID:Antioxidant vitamins in cataract prevention. 265 16

Sugar cataract formation has been demonstrated to result from lenticular sorbitol accumulation. In the lens, the activity of aldose reductase has been observed to increase with the onset of diabetes, while the activity of sorbitol dehydrogenase decreases. This shift in activities of these two Sorbitol Pathway enzymes favors the increased accumulation of sorbitol. Immunohistochemical studies with antibodies prepared against purified rat lens aldose reductase reveal a striking increase in immunoreactive positive staining for aldose reductase in lenses from diabetic rats. Two weeks after the onset of diabetes, increased immunohistochemical staining for aldose reductase appears beneath the epithelial region where water cleft formation occurs, and the intensity of this staining increases with the formation of vacuoles. By 6-8 weeks, the presence of large vacuoles and areas of liquifaction containing dense immunoreactive stain can be observed. Examination of human cataractous lenses with antibodies prepared against purified human placenta aldose reductase suggest similar increases in immunoreactive staining in the human diabetic lens. Cataractous lenses from diabetic patients revealed increased immunoreactive staining for aldose reductase, which was associated with the presence of vacuoles in both the anterior or posterior superficial cortical layers. Examination of similar vacuole containing regions from non-diabetic cataractous lenses revealed no increase in immunoreactive staining for aldose reductase. These results suggest that the enhanced activity of aldose reductase observed in diabetes is due to an increased amount of enzyme, rather than enzyme activation.
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PMID:Immunohistochemical localization for aldose reductase in diabetic lenses. 310 Apr 73

The trabeculectomy developed independently by Sugar, Vasco-Posada, Koryllos and Cairns is equivalent to a sinusotomy with an additional cyclodialysis effect if the modified technique suggested by Watson is used. About 309 cases are reported, some of which were followed up for up to 12 years. No late failures or complications were observed. Failures are due to absence of the cyclodialysis effect. Regression of a bleb often occurs without any deterioration in intraocular pressure. The development of aqueous veins and scleral vessels around the incision is not uncommon. The causal relationship between postoperative hypotension and the development or spread of cataract is discussed.
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PMID:[Extended sinusectomy (trabeculectomy with cyclodialysis effect). Late results and analysis of failures]. 372 68

Heretofore, the intracellular accumulation of sorbitol has been associated exclusively with deleterious (cataractogenic) changes in the lens. This study demonstrates a beneficial role for the sorbitol pathway in the rabbit lens, namely that of counteracting extracellular, glucose-derived, osmotic stress with the intracellular production of osmotically active sorbitol. Large and sudden increases in the extracellular glucose concentration lead to dehydration of the lens, a response that can be diminished by intracellular sorbitol and fructose production. These results are discussed in light of the impact (beneficial/detrimental) of aldose reductase inhibitors on the lens. Sugar cataract formation appears to result from continuous, rather than cyclical, activity of a pathway which normally may have a protective function in the lens.
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PMID:Sorbitol production in the lens: a means of counteracting glucose-derived osmotic stress. 380 97

Medical treatment of cataract depends on understanding the mechanism of cataract formation. This is established in sugar cataract, in which sugar is metabolised to sugar alcohol. Sugar alcohol accumulates and the resultant osmotic stress is considered to cause lens fibre damage. The conversion of sugar to alcohol is effected by the enzyme aldose reductase and interest now centres around the use of aldose reductase inhibitors. A controlled clinical trial into the effect of the spirohydantoin Sorbinil in adult diabetic cataract has started at Oxford. Aldose reductase inhibitors may also act on non-diabetic cataract, which is supported by some clinical evidence. The biochemical basis of this and other possible treatments for cataract are outlined.
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PMID:Medical therapy in the prevention of cataract. 393 85

Sugar cataracts rapidly develop in dogs fed a diet containing 30% galactose. While studies on the formation and progression of these sugar cataracts suggest that they are osmotic in nature and are linked to aldose reductase, sugar cataract formation in the dog to date has not been completely prevented by the administration of aldose reductase inhibitors sorbinil and M79175. To demonstrate that the formation and progression of sugar cataracts in galactose-fed dogs can be dose-dependently inhibited by the administration of aldose reductase inhibitors, 9-month old male beagles were placed on diet containing 30% galactose with/without 10 or 16 mg kg-1 day-1 of M79175 for up to 39 months. Cataract progression in all dogs was followed by periodic slit lamp examination and documented by retroillumination photography. Although large variations in cataract formation and progression were observed, all dogs fed a 30% galactose diet for 39 months developed cataracts. Lens changes were significantly less in galactose-fed dogs treated with either 10 or 16 mg kg-1 M79175 and no cataract formation was observed in 3 of 6 galactose-fed dogs treated with 16 mg kg-1 M79175. These observations confirm that aldose reductase plays a key role in initiating cataract formation in galactose-fed dogs and that cataract formation can be prevented by adequate inhibition of aldose reductase.
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PMID:Dose-dependent prevention of sugar cataracts in galactose-fed dogs by the aldose reductase inhibitor M79175. 953 47

The authors present current knowledge concerning the role of polyols in the formation of cataract in diabetic patients. Sugar alcohols are formed in lens as a consequence of glucose conversion in the sorbitol pathway. The pharmacological modulation of this process by the application of aldose reductase inhibitors are also discussed.
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PMID:[The role of polyol pathways in formation of diabetic cataracts]. 968 89

Several recent studies with the sorbitol dehydrogenase inhibitors 4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N, N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine , SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat. For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50% galactose. Inhibitors were administered in the diet with the diet containing 0.06% (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125% (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase inhibitors while no difference in cataract formation was observed in galactose-fed rats treated with/without SDH inhibitors. Cataract formation was inhibited in both diabetic and galactosemic rats by either Ponalrestat or AL 1576. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.
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PMID:Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats. 973 86

The relative importance of sorbitol formation versus nonenzymatic glycosylation and advanced glycosylation end products (AGEs) on sugar cataract formation was examined in diabetic rats. Diabetes was experimentally induced in young, 50 g rats with streptozotocin, and aldose reductase inhibitors were administered in the diet for up to 8 weeks at concentrations of 0.06% for tolrestat or ponalrestat and 0.0125% for AL-1576. Cataract formation was monitored by hand-held slit lamp for up to 11 weeks. Lens polyol levels were monitored by GLC, glycosylated protein levels were spectrophotometrically determined, and AGE products were estimated by fluorescence measurements and ELISA. Sugar cataract formation was observed in all untreated diabetic rats while cataract formation was inhibited in all diabetic rats treated with the AR inhibitors. Lens sorbitol levels were reduced in all ARI-treated rats. Glycosylated lens protein levels were elevated in the diabetic rats, and these levels were not significantly lower in the non-cataractous lenses from ARI-treated diabetic rats. Fluorescence measurements of the lens proteins revealed increased lens AGE levels in all diabetic rats, and these were slightly reduced in the aldose reductase inhibitor treated diabetics. With ELISA, immunoreactive AGEs were only detected in cataractous lenses from the untreated diabetic rats. Immunoreactive AGEs were not detected in the clear lenses of the aldose reductase inhibitor treated diabetics or in the non-diabetic controls. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalyzed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.
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PMID:Relative importance of aldose reductase versus nonenzymatic glycosylation on sugar cataract formation in diabetic rats. 1080 25


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