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)

Evidence linking the enzyme aldose reductase (alditol:NADP+ oxidoreductase, EC 1.1.1.21) to the pathogenesis of several diabetic complications is rapidly mounting. The results of several animal studies combined with preliminary reports of ongoing clinical trials indicate that inhibition of aldose reductase produces a beneficial effect against such diabetic complications as neuropathy, cataract, corneal epitheliopathy, retinopathy, microangiopathy, and possibly nephropathy. The observations that aldose reductase inhibitors appear to provide a new direct mode of treatment for the control of diabetic complications--a method independent of the insulin-related control of blood glucose levels--has spurred interest in the development of more potent and selective inhibitors. That goal can be more easily realized through an understanding of how these inhibitors interact with the aldose reductase protein. This requires insight into the steric and electronic requirements of both the inhibitors and the enzyme site where they bind (inhibitor site). Through the use of computer molecular modeling, molecular orbital calculations, known structure-activity relationships (SAR), protein modification reagents, and irreversible inhibitors, specific structural, and electronic similarities among the apparently structurally diverse aldose reductase inhibitors (ARIs) have been observed. In turn, these studies have led us to postulate the pharmacophor requirements of the ARI site.
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PMID:The aldose reductase inhibitor site. 308 1

The isolated cultured rat lens has been used to examine the effects of the aldose reductase inhibitor sorbinil on lenticular polyol accumulation and sugar cataract formation. Lenses incubated in medium containing 35 mmol/L glucose accumulated sorbitol over a seven-day period without the appearance of overt opacities. Sorbitol accumulation was inhibited in a dose response fashion by sorbinil with an IC50 of 3.1 X 10(-6) mol/L. In lenses incubated in the presence of 29.5 mmol/L xylose, xylitol accumulation was accompanied by an increase in the water content of the lens and the development of a classical sugar cataract. All of these effects could be prevented by the addition of sorbinil to the culture medium. Complete inhibition of cataract formation required greater than an 80% inhibition of the xylitol accumulation. Reversal of a preformed xylose cataract by sorbinil could be achieved if the inhibitor was added at the stage of cortical opacities (20 h). Cataract progression proceeded normally over the next 48 hours and then the lens slowly began to clear. The rate of the reversal was dependent on the dose of sorbinil.
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PMID:Effects of the aldose reductase inhibitor sorbinil on the isolated cultured rat lens. 308 8

Carbon-13 nuclear magnetic resonance spectroscopy has been used in the study of glucose metabolism, specifically aldose reductase inhibition, in intact rabbit lenses maintained in organ culture. This technique provides an effective method of screening potential inhibitors of aldose reductase under conditions that more closely approximate in vivo conditions than do earlier methods. The aspirin substitutes acetaminophen and ibuprofen were studied as aldose reductase inhibitors and were found to be effective in reducing sorbitol accumulation in lenses exposed to high glucose stress. Results of this work with various inhibitors of aldose reductase are discussed in terms of lens metabolism and implications regarding diabetic complications such as cataract formation.
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PMID:Study of aldose reductase inhibition in intact lenses by 13C nuclear magnetic resonance spectroscopy. 308 27

Diabetes causes cataract and certain physical changes in the lens. The diabetic lens is larger than the non-diabetic and shows greater light scatter and fluorescence. Both hyperglycaemia and lowering of blood glucose case refractive changes and hypermetropia is the most common. Classical 'snow-flake' juvenile cataract associated with hyperglycaemia is now rare. It has an osmotic mechanism. Diabetes is a risk factor for cataract in adults which is duration dependent, more frequent in women and leads to earlier surgery. It resembles non-diabetic senile cataract. Extracapsular cataract extraction is the method of choice for diabetic cataract with a better visual result and less risk of rubeosis iridis. A posterior chamber implant may still permit retinal photocoagulation if necessary. Diabetic retinopathy is still the leading cause of blindness in the working age group. The beneficial effect of photocoagulation has been shown by randomized controlled trials to be long-lasting for both proliferative retinopathy and maculopathy. Therefore there is a need for screening, especially for those with proliferative disease which may be present without symptoms. A knowledge of risk factors will enhance detection rate with duration as the strongest determinant for retinopathy. Any screening modality should be highly sensitive as well as specific. The role of different professionals as potential screeners should be considered. Adequate provisions include facilities for checking vision and for dimming ambient lighting. Mydriasis and a good ophthalmoscope light will increase detection rate. The use of a 45 degrees non-mydriatic camera is unlikely to supplant the use of an ophthalmoscope as a single field is likely to miss important lesions. A 60 degrees camera may confer a large enough field and the use of transparencies will provide magnification when films are projected but the camera is more difficult to use. A list of features chosen by a recent study to characterize sight-threatening retinopathy is included and their presence indicates the need for referral to an ophthalmic clinic for treatment or close observation.
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PMID:Cataract and retinopathy: screening for treatable retinopathy. 309 17

Increased blood sugar levels may influence the refractive power of the lens in juvenile diabetics, and can lead to the rare true diabetic cataract ("snow-storm cataract"). Surplus glucose induces accumulation of the sugar alcohol within the cells, thus generating disturbances of the osmotic balance and finally causing cataract. The enzyme aldose reductase catalyzes the formation of sorbitol. Experiments with animals have shown that aldose reductase inhibitors can prevent the formation of such opacities with streptozotocin-induced diabetes in rats. Numerous aldose reductase inhibitors are now known, but we still have insufficient knowledge to determine whether systemic or local administration is preferable. The mechanisms reported here are not relevant with respect to the frequent occurrence of senile cataract in older diabetics, which has often been described.
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PMID:[Aldose reductase inhibitor--a new way for preventing diabetic lens changes?]. 310 Aug 60

The role of reduced glutathione (GSH) in lens membrane function was studied by depleting GSH with 1-chloro-2,4-dinitrobenzene (CDNB), a reaction catalyzed by GSH-S-transferase. Depletion of GSH in the lens epithelium by 70-90% led to a decrease in uptake and increase in efflux of 86Rb. ATP levels and Na+/K+-ATPase activity were normal while there was a slight decrease in lactate production. The results provide the first direct evidence that depletion of endogenous GSH per se does not lead to inactivation of Na+/K+-ATPase. However, lenses deficient in GSH when challenged with a normally tolerated level of H2O2 showed significant inactivation of membrane ATPase without a further increase in membrane permeability. Pretreatment with CDNB resulted in a 3-fold stimulation of the hexose monophosphate shunt activity which is attributed to the unexpected finding of a significant increase in the level of oxidized glutathione in the lens. It is concluded that deficiency of GSH causes a marked increase in membrane permeability and such lenses are susceptible to oxidative damage resulting in inactivation of the Na+/K+ pump, thus leading to ionic changes and cataract development.
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PMID:Effect of glutathione depletion on cation transport and metabolism in the rabbit lens. 318 92

The effects of several intraocular irrigating solutions on the rate of glycolysis and the levels of ATP and glutathione in the isolated rat retina were investigated. The media were HCO3-Ringer, balanced salt solution (BSS) (to which 5 mM glucose was added), and BSS PLUS. There were no significant differences in the metabolic activities and metabolite levels in retinas incubated with either HCO3-Ringer or BSS PLUS. Retinas incubated with BSS PLUS had higher rates of aerobic and anaerobic glycolysis and more ATP than did retinas incubated with BSS. There were no significant differences, however, in the glutathione content of retinas incubated with BSS PLUS and BSS. These results show that retinal energy metabolism is maintained better with BSS PLUS because this irrigating solution contains glucose and bicarbonate.
J Cataract Refract Surg 1988 Nov
PMID:Comparison of intraocular solutions on glycolysis and levels of ATP and glutathione in the retina. 323 May 16

Almost all the male animals of WBN/Kob rat strain show the diabetic syndrome whereas none of the female animals develop such diseased conditions even at elder age. We investigated the effect of sex hormones on the onset of diabetic syndrome of this rat strain by comparing the results of body weight gain and various clinical tests such as glucose tolerance, serum biochemistry and histopathology of spayed female rats with those of non-treated and sham-operated female animals kept until 88-week-old. Non-treated and sham-operated female animals had shown no abnormal result even at 88-week-old. Spayed female animals began to reveal glucosuria associated with polydipsia and polyuria from 72-week-old, and gradually developed emaciation and cataract. Increased body weight gain, impaired glucose tolerance and lasting hyperglycemia were observed prior to the onset of the symptoms. Pancreatic changes consisted of atrophy of acinar tissue and atrophy or disappearance of islet tissue attributable to clinical data also were detected in spayed female animals. These diabetic syndrome and pancreatic change were analogous to those of aged male WBN/Kob rats but the onset of spayed females was delayed and less severe. Present results suggest that female sex hormones are protective from the onset of diabetic syndrome of WBN/Kob rats.
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PMID:[Effect of gonadectomy on the onset of diabetic syndrome in the female WBN/Kob rats]. 324 Jul 81

We present two cases of Werner's syndrome associated with intracranial meningioma. Characteristic clinical features of Werner's syndrome include short stature with slender extremities, premature senility, juvenile cataract, skin changes, a tendency to diabetes mellitus and familial occurrence. A 44-year-old female, who had been treated for diabetes mellitus, was diagnosed as having Werner's syndrome because of various characteristic features. A falx meningioma was incidentally found on CT scan, and was surgically removed. Her diabetes mellitus improved. The second case was a 28-year-old male was diagnosed as having Werner's syndrome, diabetes mellitus, juvenile cataract, together with diabetes insipidus, and liver dysfunction. He developed severe headache, gait disturbance and then became unconscious with right hemiparesis. He was found to have a parasagittal meningioma by CT scan and angiography. After removal of the tumor, diabetes mellitus, diabetes insipidus and liver dysfunction improved. The reported incidence of neoplasms associated with Werner's syndrome is about 10%. The majority of associated tumors were mesenchymal in origin. Ten meningiomas, 1 neurinoma and 2 gliomas are reported as associated tumors in the central nervous system. Most of the associated meningiomas were asymptomatic and found incidentally at autopsies or CT scans. Diabetes mellitus associated with Werner's syndrome is generally mild with high immunoreactive insulin value and is controllable by diet therapy and oral antidiabetic drugs. Daily profile of blood sugar improved after the removal of tumor in our cases. In 50 gm glucose tolerance test, tendency of delayed appearance of peak value, which is common in Werner's syndrome, was not altered in our cases. Discussion is made as to the association of Werner's syndrome with meningioma and diabetes mellitus.
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PMID:[Werner's syndrome associated with meningioma: case report]. 328 33

Radioactive galactose becomes attached covalently to lens proteins in the same way as glucose. Simultaneous incubation with aspirin inhibits the reaction with galactose in a dose-related manner. Incubation with aspirin before incubation with galactose in the absence of aspirin showed that aspirin can modify crystallins permanently to prevent the binding of galactose. The galactosylation was also inhibited by glutathione at physiological concentrations. All major groups of lens proteins reacted with galactose but a higher level of modification of protein in the material of high molecular weight may indicate that galactosylation has induced aggregation of the proteins. The modification of all major crystallin groups was confirmed by isolating the galactosylated proteins by affinity chromatography. The results are discussed in relation to glycosylation of lens proteins in diabetes and galactosaemia and the role of glycosylation in cataract.
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PMID:Non-enzymic glycosylation (glycation) of lens proteins by galactose and protection by aspirin and reduced glutathione. 340 87


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