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

Cataracts removed intracapsularly by cryoprobe technique from human diabetics were analyzed for sugars and polyols by gas liquid chromatography. The contents of sorbitol and fructose of lenses followed blood glucose levels at least up to 250 mg/dl. Studies indicate that human lens is capable of synthesizing substantial amounts of polyol pathway metabolites given exposure to high glucose levels such as are prevalent in diabetes. The synthesis of sorbitol was found to be susceptible to quercitrin, an inhibitor of aldose reductase. The implications of these findings in the formation of cataracts in diabetic individuals have been discussed.
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PMID:Implications of aldose reductase in cataracts in human diabetes. 10 20

Bovine lens aldose reductase, an enzyme important in sugar cataract formation, has been purified using a new procedure, and its optimum conditions of assay defined in both lens homogenates and purified preparations. Preliminary kinetic analysis shows that the degree of the rate equation is of a low order, and may be Michaelian under the standard conditions used.
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PMID:Kinetic behaviour under defined assay conditions for bovine lens aldose reductase. 11 91

Immediately after cataract extraction, lenses from diabetic and nondiabetic patients were collected, classified, and assayed or incubated in high-glucose medium. The distribution of cataract types within the diabetic and nondiabetic groups was almost identical. The aldose reductase (AR) inhibitor AY22,284 (Alrestatin) was as effective in blocking sorbitol formation in diabetic as in nondiabetic lenses. While there was no difference in the level of intralenticular glucose, the diabetic lens produced significantly more sorbitol than did the nondiabetic lens. Also, the activity of polyol dehydrogenase (PD) was much lower in the diabetic population. The diabetic lenses swelled slightly more (P <.2) than nondiabetic lenses in high glucose media, and AY22,284 was effective in reducing the swelling of diabetic lenses in 35.5 mM glucose medium. While these results are preliminary, they suggest that diabetes, in some way, may confer on the human lens an increased susceptibility to osmotic stress via the sorbitol pathway. It is also reassuring to note that an AR inhibitor is no less effective in blocking the more active AR in the diabetic than in the nondiabetic lens. The therapeutic implications of this are discussed.
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PMID:Efficacy of Alrestatin, an aldose reductase inhibitor, in human diabetic and nondiabetic lenses. 12 68

In some tissues containing aldose reductase, increased flux through the polyol pathway has been implicated as being causative in diabetic complications (e.g., cataracts, peripheral neuropathy). We have found CP-45,634 (d-6-fluoro-spiro[chroman-4,4'-imidazolidine]-2',5'-dione) to be a highly potent, structurally novel, uncompetitive inhibitor of calf lens aldose reductase (IC50 approximately 5 X 10(-7)M). In a system in which sorbitol accumulation in isolated rat sciatic nerves was monitored in the presence of high (50 mM) glucose concentrations, CP-45,634 produced inhibition of polyol accumulation at levels as low as 1 X 10(-6)M. To determine if in vitro activity would translate to in vivo models, sorbitol accumulation in rat sciatic nerves was measured 27 hr after induction of diabetes with streptozotocin. Orally administered CP-45,634 was effective at dose levels as low as 0.25 mg/kg, t.i.d., and at 0.75 mg/kg produced an 85% inhibition of sorbitol accumulation. Two weeks after induction of diabetes by streptozotocin, sorbitol levels in rat lens and the sciatic nerve rose to 21,203 nmole/gm and 1,161 nmole/gm, respectively. Subsequent oral administration of CP-45,634 (2.5 mg/kg, b.i.d.) for 1 wk reduced these levels by 92% in nerves and 90% in lenses. In galactosemic rats, CP-45,634 inhibited the rise in lens galactitol and effectively delayed cataract formation at oral doses as low as 5 mg/kg/day. These high levels of in vivo activity suggest that CP-45,634 has potential for assessing the role of the polyol pathway in diabetic complications.
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PMID:CP-45,634: a novel aldose reductase inhibitor that inhibits polyol pathway activity in diabetic and galactosemic rats. 12 97

Oral administration of quercitrin, an inhibitor of aldose reductase, leads to a significant decrease in the accumulation of sorbitol in the lens of diabetic Octodon degus. The onset of cataract is effectively delayed when quercitrin is continuously administered. Thus in these diabetic animals, as in galactosemic rats, the use of an effective aldose reductase inhibitor impedes the course of cataract development. These observations support the hypothesis that in diabetes, as in galactosemia, aldose reductase plays a key role in initiating the formation of lens opacity.
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PMID:Diabetic cataracts and flavonoids. 40 44

Diabetes is known to be associated with an increase in aldose reductase activity, platelet hyperaggregability, lipid peroxidation, and cataract formation. A molecule, D-myo-inositol 1,2,6-trisphosphate (PP-56), derived from phytic acid, could in principle, by supplying myoinositol to tissues and acting as an antioxidant, counteract some of the manifestations of diabetes. Thus, the effects of PP-56 on platelet aggregation, fatty acids, and polyols were investigated in uncontrolled streptozotocin-induced diabetes in rat in relation to cataract and lipid peroxidation. A decrease in the response of platelet aggregation to thrombin and ADP (P less than 0.05, P less than 0.001) and in the level of sorbitol and the ratio sorbitol/myo-inositol (P less than 0.01) in platelets was observed in the rats treated by PP-56 for 7-8 weeks. These beneficial effects were associated with an incidence of cataract reduced by 26 to 44% (P less than 0.05 to P less than 0.001) depending on the duration of treatment. They were also accompanied by a significant lower plasma level of malondialdehyde (P less than 0.05), and, more markedly, of conjugated dienes (P less than 0.001) as well as an increase in platelet lipids of the 20:4(n-6)/20:3(n-6) ratio, an index of delta 5 desaturase activity. PP-56 appears to modulate fatty acid desaturases and aldose reductase in platelets and delay by a few weeks the development of cataract in this acute model of diabetes.
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PMID:Effect of D-myo-inositol on platelet function and composition and on cataract development in streptozotocin-induced diabetic rats. 138 35

We have shown that galactose cataract development is delayed or inhibited with the administration of aldose reductase inhibitors (ARIs). Dulcitol forms and accumulates in the lens of rats fed galactose. We undertook investigations to study the effectiveness of ARIs in preventing the formation and accumulation of dulcitol in the lens. Young Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15 mg sorbinil, 0.15, 0.5, or 1.0 mg E-0722/day/Kg body weight. At desired intervals following the initiation of diets, the lenses were processed for the determination of galactose and dulcitol levels. The lenticular dulcitol increased significantly in all animals fed galactose reaching a maximum level by approximately 15 days with comparatively lower levels in the groups fed ARIs with galactose; this increase was dose dependent in the groups fed E-0722. There was a subsequent, rapid drop in lenticular dulcitol by 18 days in all dietary groups. Interestingly, a second peak of increased lenticular dulcitol was observed in all groups. The correlation between dulcitol accumulation and cataract development is discussed.
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PMID:Effect of aldose reductase inhibitors on lenticular dulcitol level in galactose fed rats. 145 83

The Emory mouse is presumed to be a model for studies on human senile cataracts. The cataract develops in 5-8 months after birth, and it does not appear to have an osmotic component. To date, no specific metabolic lesion has been uncovered as a probable cause to this cataract. Several studies have shown that the Emory mouse undergoes accelerated aging changes, possibly leading to development of senile-type cataracts. In this study we quantitated changes that might occur in the population of various mRNAs for proteins presumed to be essential for lens transparency, and for proteins that may contribute to development of cataracts. By Northern blot hybridization analysis we quantitated the mRNAs for: alpha A-crystallin, beta B1-crystallin, gamma-crystallin, the main lens intrinsic membrane protein, MP26, and aldose reductase; all in lenses of Emory mouse early cataract strain (EMEC), and of an age-matched cataract resistant strain (CR). These measurements were done in increments of 1 month over a 6-month period, then at both 9 and 12 months. The results show that all of these mRNAs decrease with age and with development of cataracts; although in some cases the initial concentrations at 1 month appear to be lower in the EMEC than in the CR strain. The most dramatic change occurred with the MP26 mRNA. In the CR strain, MP26 mRNA maintained its high concentration for a period of about 6 months before it began its decline to the 12 month level (about 25% of the 1 month level).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Profile of messenger RNA decay in the Emory mouse lens in cataractogenesis and in aging. 148 8

Cataract is the major cause of blindness worldwide and at present the only approved treatment in many countries including the UK and USA is surgical removal of the lens. In other countries various anti-cataract drugs are available without proof of their efficacy. Research is continuing into the possible benefits of several groups of drugs and some vitamins. The first to be studied were sorbitol-lowering agents (aldose reductase inhibitors) based on the sorbitol hypothesis for diabetic cataract. Sorbitol-lowering agents have distinct effects in vitro and many of them delay the development of cataract in galactose-fed rats. A few delay cataract in diabetic rats but none have been proved effective in clinical trials, although these continue. Aspirin, paracetamol (acetaminophen) and ibuprofen delay diabetic cataract in rats, and have been shown to delay other experimental cataracts. Case-control studies from 3 continents indicate that these drugs, or at least aspirin, protect against cataract. Results of studies on all 3 drugs indicate a benefit even at low doses. Population-based studies did not identify any protection against early lens opacities but tiny opacities that do not impair vision are not a problem. Bendazac protects lens proteins in vitro and delays cataractogenesis in x-irradiated rats. In humans, it reached the clinical trial stage but most trials have been small and with subjective criteria of opacification. One objectively monitored trial suffered from a high drop-out rate. Other preparations studied less extensively include vitamins, aminoguanidine to prevent protein cross-linking in diabetes and agents designed to boost glutathione levels. It is probable that some agents which may delay or prevent cataract will be proved effective soon, and in the end there may be different drugs to delay cataract in different high risk groups. This is what might be expected of a multifactorial disease, although compounds that intervene in the final common pathways to cataract could have a broad efficacy.
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PMID:Pharmacological treatment strategies in age-related cataracts. 150 43


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