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)

Aldose reductase (AR) appears to initiate the cataractous process in galactosemic and diabetic animals. Sugars in excess are converted to polyols by lens AR. In sugar cataracts, polyols accumulate to levels substantial enough to cause a hypertonicity leading to lens fiber swelling. All other changes appear secondary to polyol accumulation and lens swelling. The development of sugar cataracts can be duplicated in organ culture. In culture, the various changes that occur were minimized or did not occur when inhibitors of AR were included in the medium. Moreover, AR inhibitors were shown to effectively delay the onset of sugar cataract development in animals. A defect in the corneal epithelium of diabetics became apparent in vitrectomy. One manifestation of this problem was the delay in the reepithelialization of denuded corneas. In examining this problem experimentally, the epithelium was removed from the corneas of diabetic and normal rats. The regeneration of epithelium in corneas of diabetic rats required a longer period than in the normal. The possibility that AR, active in the epithelium, was involved in this phenomenon was investigated. The corneal epithelium was removed from both eyes of a diabetic rat. One eye was treated topically with the AR inhibitor CP-45,634 while the other served as control. The eye treated with CP-45,635 regenerated epithelium much more quickly than the untreated eye. Other AR inhibitors had similar beneficial effects.
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PMID:Aldose reductase in diabetic complications of the eye. 4 23

Aldose reductase (AR) and sorbitol dehydrogenase (SDH) make up the sorbitol pathway, which has been implicated in the pathogenesis of sugar cataracts. The levels of the two enzymes were determined with quantitative histochemical techniques in the epithelium, cortex, and nucleus of normal and diabetic rat lenses. The ratio of activity of AR to SDH was found to be nearly 50 to 1 in all substructures. This would strongly favor sorbitol accumulation and subsequent cataract formation.
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PMID:Aldose reductase and sorbitol dehydrogenase distribution in substructures of normal and diabetic rat lens. 40 52

Aldose reductase inhibitors (ARIs) have been known to be effective in preventing galactose cataract by blocking the polyol pathway. Because the rat congenital galactose cataract is also induced by accumulated polyol, the effect of an ARI in the induction of congenital galactose cataract was investigated. Pregnant rats were placed on a 30% galactose diet. On fetal day 16, 17, 18 or 20, the fetal lenses were examined by light microscope. Lenses from newborn rats with mothers fed galactose diet until gestational day 16, 17, 18 or 20 and then given a galactose diet containing ARI were also examined. The fetal lenses obtained from galactose-fed mother rats on day 16 of gestation were morphologically similar to those of controls. On day 17, the experimental lenses displayed vacuolated areas. The lenses of newborn rats with mothers given an ARI diet after gestational day 16 showed no morphological changes, while a few small vacuoles were observed in the lens of rats with mothers given the ARI diet after day 17, 18 or 20 of gestation. ARI inhibited the rat congenital galactose cataract even when the drug was given to the mother rat during a late stage of pregnancy.
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PMID:Inhibition in rat of development of in utero galactose-induced cataract by an aldose reductase inhibitor--a light microscopic study. 177 Jun 72

Aldose reductase activity can be measured in the neutrophil and it has been proposed that this may be a marker for risk of complications in diabetes. We have studied aldose reductase activity in neutrophil, nerve, and lens in diabetic patients undergoing sural nerve biopsy or cataract extraction. A correlation was demonstrated between lens and neutrophil aldose reductase activity (r = 0.53, p = 0.01) but no correlations were demonstrated between nerve aldose reductase activities and nerve morphometry, nerve function or neutrophil aldose reductase activity. No significant difference was found between neutrophil aldose reductase activities in groups of patients with severe neuropathy, or cataract, or no complications (24 (interquartile range 16-32) vs 24 (16-40) vs 24 (16-40) nmol NADPH min-1 10(8)-cells-1). In a group of 56 Type 1 diabetic patients screened within 6 years of diagnosis, multiple regression analysis failed to show any relationship between neutrophil aldose reductase activity and abnormalities of neurophysiological function. These results suggest that neutrophil aldose reductase activity cannot be used as a marker for the development of cataract or neuropathy in diabetes.
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PMID:Neutrophil aldose reductase activity as a potential marker for neuropathy and cataract in diabetes. 183 41

As the UV-B cataract and early stages of diabetic cataract in rats only touches the epithelium and anterior superficial cortex, a whole lens analysis is not meaningful, but a regional analysis with the freeze-sectioning device has to be performed. Scheimpflug photography with microdensitometric image analysis enables the scientist to discern in vivo single layers along the optical axis of the lens. UV-B cataracts (0.2 J/cm2, every 2nd day) and diabetic cataracts (Streptozotocin (STZ), 70 mg/kg BW) were induced in Brown-Norway rats. The stages of lens opacification were documented by Scheimpflug photography. 8 weeks after start of UV-B treatment and at several dates before onset of visible diabetic cataractous changes, the animals were sacrificed. The lenses were divided reproducibly into 4 or 7 parts such as an equatorial ring and several layers of the central cylinder from anterior to posterior part. The enzyme activity spectrum shows highly region related pattern that would not have been found in a whole lens analysis. Aldose reductase was activated before appearance of visible cataractous changes due to diabetes compared to normal lenses. In contrast Fructose-1,6-biphosphate-aldolase activity was lower before onset of visible changes than in normal lenses, but only within the 1st section where later visible cataractous changes of UV-B cataract could be detected.
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PMID:Regional enzymatic analysis of UV-B and streptozotocin induced diabetic cataract lens. 196 39

Aldose reductase (AR) is an enzyme which catalyzes the transformation of D-glucose to sorbitol. Under non physiological conditions, like diabetes for example, the accumulation of polyols in the lens, sorbitol in particular, gives a basis to the osmotic hypothesis of cataract formation. AR inhibitors can protect against such accumulation. Oxidation of the constituents of the lens is a primary phenomenon in cataract formation, and some authors have suggested that the autoxidation of monosaccharides would originate the formation of cataract. For these authors, AR inhibitors would act by trapping the radical intermediates formed, inhibiting the denaturation of proteins in the organ and the lowering of glutathione. There classes of AR inhibitors can be distinguished: flavonoids and their related compounds, spirohydantoins--like sorbinil--and related compounds, and compounds with an acid function such as alrestatine. For each of these three classes, the authors try to establish the structure-activity relationship of the molecules. The possibility of a single site of interaction between AR and the different AR inhibitors is discussed. Differences in the inhibitory effect for a given compound between species, and for one species between tissues have been underlined.
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PMID:[Aldose reductase inhibitors]. 310 88

Aldose reductase is implicated in the pathogenesis of diabetic cataracts; therefore, inhibition of this enzyme subsequent to cataractogenesis may represent a therapeutic approach for restoration of lens physiology. In the present study, the effect of aldose reductase inhibition subsequent to stage I cataract formation was investigated in the streptozocin-induced diabetic rat. Our results indicated that the aldose reductase inhibitor sorbinil, a spirohydantoin, arrested further progression and promoted a reparative process despite continuation of hyperglycemia and elevated lens glucose. Quantitative analysis of scanning electron micrographs indicated that the afflicted lens regions were contained and their cellular components stabilized with regard to fiber hydration and interdigitation. The reparative process included: normalization of lens sorbitol, gradual recovery of existing fiber contour and interdigitation, production of new fibers, and partial restoration of lens myo-inositol content.
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PMID:Reversal of diabetic cataract by sorbinil, an aldose reductase inhibitor. 391 57

Aldose reductase is implicated in the pathogenesis of sugar cataracts; therefore, inhibition of this enzyme subsequent to cataractogenesis may represent a therapeutic approach for the restoration of lens physiology despite the persistence of diabetes or galactosemia. In the present study, the effect of aldose reductase inhibition subsequent to stage-I cataract formation was investigated in the galactose-maintained rat. Our results indicated that despite continuation of galactose feeding the aldose reductase inhibitor, Sorbinil, a spirohydantoin, arrested further progression and promoted a reparative process. Quantitative analysis of scanning electron micrographs indicated that the afflicted lens regions were contained and their cellular components stabilized with regard to fiber hydration and interdigitation. The reparative process involved: decrease in lens dulcitol, gradual recovery of fiber thickness and partial restoration of lens myo-inositol content. At this stage of cataractogenesis, despite continuance of galactose feeding, the effects of Sorbinil treatment were comparable to the reparative process achieved by restoration of a normal diet.
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PMID:Reversal of stage-I sugar cataract by Sorbinil, an aldose reductase inhibitor. 392 28

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

A variety of agents are currently available that claim to either prevent, delay, or reverse cataracts associated with aging (senile cataracts), radiation, or diabetes and galactosemia (sugar cataracts). Senile cataract therapy includes formulation containing inorganic salts, nutritional supplements, natural product extracts, sulfhydryl, and sulfonic acid containing compounds and miscellaneous redox and nonsteroidal anti-inflammatory compounds. Agents associated with the treatment of radiation cataracts include anti oxidants and free radial scavengers. Aldose reductase inhibitors have been effective in the prevention of sugar cataracts. A summary of these agents and their potential ocular effects are presented.
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PMID:Overview of the current attempts toward the medical treatment of cataract. 634 28


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