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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracapsular cataracts obtained within 3 h after surgical extraction were photographed with the CCRG technique and immediately subjected to fluorescence spectroscopy followed by 31P- and 13C-nuclear magnetic resonance (NMR) spectroscopy. Fluorescence spectroscopy demonstrates an excellent correlation between nontryptophan fluorescence intensities and lens color. An interesting correlation was also observed between the degree of light scatter as determined by the 290-nm excitation peak for intrinsic lens tryptophan fluorescence and the CCRG (photographic) appearance of these cataractous lenses. Based on 100 cataracts analyzed, there is a strong correlation between this kind of light scattering measurement and the type and degree of lens opacification. A similar correlation is evident with the 31P-NMR organophosphate profiles in the lenses in which the sugar phosphate levels are elevated only in diabetic patients with cataracts ('diabetic cataracts'). Aside from fluorescence and 31P-NMR spectroscopy, selected lenses were also incubated with 5.5 nM 13C-glucose as soon as they were obtained, and the foregoing spectroscopy was performed, followed by 13C-NMR analyses to detect and monitor for sorbitol accumulation in young versus old normal lenses and in diabetic cataracts. These studies clearly demonstrate a direct correlation between nontryptophan-fluorescent chromophore levels, light scattering (determined by tryptophan excitation peaks), lens age and cataract type. In addition, the organophosphate profiles clearly delineate the diabetic cataracts, and the 13C-NMR spectra correlate well with the age-related decrease in aldose reductase activity.
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PMID:Photographic and spectroscopic correlations of human cataracts. 271 Apr 94

Increases in corneal endothelial cell polymegathism and pleomorphism are characteristic of diabetic human and dog corneas. This study investigated the rat as a model for age- and diabetes-related changes in endothelial cell morphology. As in most mammals, aging of the normal rat results in a progressive decrease in cell density as well as reduced numbers of hexagonal endothelial cells and increased coefficient of variation of cell size after age 34 weeks. Streptozotocin-induced diabetes produced an early progressive increase in the coefficient of variation of cell size and decrease in percentage of hexagonal cells so that diabetic rats were significantly different from age-matched normal rats by 24 weeks of age. Topical treatment with the aldose reductase inhibitor, AL 1576, begun immediately after diabetes induction, prevents endothelial cell changes and cataract formation. Topical aldose reductase inhibition also reverses endothelial cell changes when treatment is begun 8 weeks after streptozotocin injection. These results indicate that the rat is a good model for studying diabetes-induced corneal endothelial changes and that topical aldose reductase inhibitors may be effective in preventing or reversing diabetic corneal endothelial cell changes.
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PMID:Corneal endothelial morphology in the rat. Effects of aging, diabetes, and topical aldose reductase inhibitor treatment. 296 59

Rat lenses with experimentally induced cataract (either by naphthalene or by streptozotocin) were analyzed biochemically. Both noxae had some effects in common. Water-soluble protein and aldose reductase activity decreased, and glucose-6-phosphate dehydrogenase, phosphofructokinase and glutathione reductase activity increased. A specific effect of streptozotocin was the rise in glucose, fructose and sorbitol. A specific effect of naphthalene was increased amounts of water-insoluble protein.
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PMID:Alterations of lens metabolism with experimentally induced cataract in rats. 297 80

The activity of the polyol pathway--a non insulin-dependent metabolic pathway of glucose--is increased in diabetic patients. Polyol accumulation is involved, by a myoinositol-dependent mechanism, in the pathogenesis of some degenerative complications of diabetes. Thus, sorbitol accumulation in the eye lens and in nerves seems to be an important factor in the development of cataract and in the slowing down of nerve conduction. Recent studies suggest that the polyol pathway may play a role in early structural abnormalities of retinal and renal microangiopathy. Synthetic aldose reductase inhibitors could be used for a physiopathogenic treatment of these complications, but the first trials in diabetic neuropathy proved disappointing. Further studies, prolonged and well controlled, are necessary to pronounce on the future of this new category of drugs.
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PMID:[Role of the polyol pathway in the occurrence of degenerative complications of diabetes]. 301 8

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

Cataracts associated with diabetes and galactosemia are characterized by their rapid onset and bilateral appearance. These cataracts display similar morphology and histology and have common biochemical mechanisms initiating the cataractous processes. An understanding of these biochemical mechanisms have been aided both by the ability to reproduce these cataracts in various animal models and by the development of potent inhibitors of aldose reductase. This is a US government work. There are no restrictions on its use.
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PMID:The effect of aldose reductase and its inhibition on sugar cataract formation. 308 4

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

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

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


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