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

Blindness in diabetics is largely due to retinopathy and/or cataract. Hyperglycaemia and the duration of diabetes are major risk factors for the development of cataract and retinopathy. This review details some of the reactions of glucose that are relevant to the development of complications, and follows the elucidation of monosaccharide autoxidation and its relevance to the aldose reductase reaction and its determination. Inhibitors of this 'aldose reductase' reaction are shown to have a number of effects which may be of importance to their action in vivo. The pharmacological implications of chemotherapy for diabetics with complications are briefly discussed.
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PMID:Aldose reductase inhibitors and cataract. 190

Naphthalene feeding can result in cataract formation in rats and rabbits due to specific metabolites of naphthalene. The concomitant administration of the aldose reductase inhibitor Al1576 to naphthalene-fed rats was proven to prevent cataract formation. To determine whether this effect was directly linked to the ability of Al1576 to inhibit enzyme aldose reductase, a variety of structurally diverse aldose reductase inhibitors, including the carboxylic acids tolrestat, Ponalrestat, and FK366, and the spirohydantoins, sorbinil and Al1576, were investigated for their ability to inhibit naphthalene-induced cataracts. Brown Norway rats, administered naphthalene by gavage, were fed normal rat chow containing these aldose reductase inhibitors at levels known to inhibit sugar cataract formation. The lens changes in these rats were monitored over a 90-day period by portable slit-lamp microscopy and histologic study. Al1576 showed a dose-dependent reduction in naphthalene-induced cataract formation, with no naphthalene-associated deposits seen in toluidine blue-stained lens sections. Sorbinil also reduced lens changes, whereas tolrestat, Ponalrestat, and FK366 had no effect. These results suggest that inhibition of naphthalene-induced cataract formation by structurally diverse aldose reductase inhibitors was not linked to the inhibition of aldose reductase.
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PMID:Effect of aldose reductase inhibitors on naphthalene cataract formation in the rat. 190 36

Young beagle dogs were fed a 30% galactose diet, with or without the aldose reductase inhibitors sorbinil or M79175. Cataract formation was monitored by indirect ophthalmoscope and hand-held slit-lamp microscopy and documented by retroillumination photography. In these dogs, the first sign of cataract development was an accentuation of the anterior and posterior lens sutures (1 month after feeding), then the appearance of cortical vacuoles (3 months after feeding), and finally, the formation of predominantly equatorial cortical opacities toward the posterior cortices (4-6 months after feeding). After long-term galactose feeding, a progressive, irregular, clear zone formed at the cortical equatorial regions. Light microscopic examination of these lenses shows that the cataracts are osmotic, many of the lens fibers appear to be swollen or ruptured, and vacuoles are seen near the bow region. Moreover, these histologic changes were reduced in a dose-dependent manner in galactose-fed dogs concomitantly treated with the aldose reductase inhibitors sorbinil or M79175. The osmotic nature of these cataracts and the observation that their formation can be reduced in a dose-dependent manner by aldose reductase inhibitors are consistent with the concept that the aldose-reductase catalyzed formation of polar sugar alcohols (polyols) initiates sugar cataract formation in the dog.
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PMID:Progression of sugar cataract in the dog. 190 66

The prophylactic effects of a new aldose reductase inhibitor (ARI), FR74366 on streptozotocin-induced rat diabetic cataract were examined by means of proton nuclear magnetic resonance (1H-NMR) relaxation time. We compared the findings with the histological finding, and it was recognized that longitudinal and transverse relaxation times (T1, T2) were prolonged before the histological changes appeared. The ARI, FR74366, prevented histologic changes and had detected by the 1H-NMR method. The results showed that 1H-NMR could be useful in the early detection of human diabetic cataract and the evaluation of the effectiveness of anti-cataract agents, for example, AR inhibitors.
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PMID:[Quantitative study of rat diabetic cataract, by the relaxation times of nuclear magnetic resonance]. 190 17

Reviewed are (1) the biochemical basis and pathophysiology of diabetic complications and (2) the structure-activity relationships, pharmacology, pharmacokinetics, clinical trials, and adverse effects of aldose reductase inhibitors (ARIs). ARIs are a new class of drugs potentially useful in preventing diabetic complications, the most widely studied of which have been cataracts and neuropathy. ARIs inhibit aldose reductase, the first, rate-limiting enzyme in the polyol metabolic pathway. In nonphysiological hyperglycemia the activity of hexokinase becomes saturated while that of aldose reductase is enhanced, resulting in intracellular accumulation of sorbitol. Because sorbitol does not readily penetrate the cell membrane it can persist within cells, which may lead to diabetic complications. ARIs are a class of structurally dissimilar compounds that include carboxylic acid derivatives, flavonoids, and spirohydantoins. The major pharmacologic action of an ARI involves competitive binding to aldose reductase and consequent blocking of sorbitol production. ARIs delay cataract formation in animals, but the role of aldose reductase in cataract formation in human diabetics has not been established. The adverse effects of ARIs include hypersensitivity reactions. Although the polyol pathway may not be solely responsible for diabetic complications, studies suggest that therapy with ARIs could be beneficial. Further research is needed to determine the long-term impact and adverse effects of ARIs in the treatment of diabetic complications.
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PMID:Potential use of aldose reductase inhibitors to prevent diabetic complications. 211 49

Preventional and reversal effects of a new aldose reductase inhibitor FR74366 on the rat galactose cataract were examined biochemically and light microscopically. A high concentration (0.075%) FR74366 showed sufficient effects both to prevent and reverse cataract, but low concentrations (0.025%) FR74366 was not effective as 0.075% FR74366. These results indicate that FR74366 can be useful drug for cataract.
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PMID:[Preventional and therapeutic effects of aldose reductase inhibitor FR74366 on rat galactose cataract]. 211 32

The development of the concept that aldose reductase (AR) is involved in diabetic complications is presented from its early beginning when Dr Van Heyningen first found polyols in sugar cataracts in 1959. The involvement of the polyol theory of sugar cataract is described. The prevention of sugar cataract formation by aldose reductase inhibitors dramatically demonstrates the role of this enzyme in sugar-induced cataracts. The possibility of AR involvement of other diabetic complications was an obvious extension of the polyol theory. The use of AR inhibitors in preventing diabetic changes in nerve and retina in animals strongly suggest that AR may play a role in the development of other diabetic complications.
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PMID:A thirty year journey in the polyol pathway. 211 48

Effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), on galactose-induced cataract formation in rats were investigated. Rats fed a 30% galactose diet developed lenticular opacity in the peripheral region by the 6th day of galactose feeding and showed gradual progression of opacity from the equator to the center of lenses. Histological study on the 15th day showed apparent lens fiber swelling and vacuolation predominantly in the equatorial and anterior cortical regions. Biochemical changes such as accumulation of galactitol, depletion of myo-inositol and decrease in glutathione (GSH) content in lenses preceded the appearance of opacity. Remarkable increase in NADPH content and decrease in NADP+ content, in addition to elevation of the ratio of Na+/K+, in lenses were also observed on the 15th day. Both M16209 and M16287 (10, 30 and 100 mg/kg/day, p.o.) dose-dependently ameliorated these morphological and biochemical changes except that restoration of myo-inositol content was incomplete. These results indicate that M16209 and M16287 can prevent galactose-induced cataract formation through amelioration of metabolic disorders and thus have high potential for clinical use in the treatment of some diabetic complications.
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PMID:Effects of novel hydantoin derivatives with aldose reductase inhibiting activity on galactose-induced cataract in rats. 212 52

It has been suggested that sugar cataracts associated with diabetes mellitus result from the accumulation of excess sorbitol within lens fibrils. Swelling of lens fibrils occurs when water moves in to maintain osmotic balance; the excess water causes disruption of fibrils and cataract formation. Other studies have indicated that more than sorbitol-induced osmotic stress is involved. Our study used lenses collected from rats after 21 or 44 d of streptozotocin diabetes. Cataracts formed in untreated 44-d streptozotocin diabetic rats, but were not apparent in the 21-d untreated diabetic animals. Lens sorbitol increased in the diabetic animals both before and after cataract formation. Lens taurine varied inversely with the sorbitol content in a fashion that resulted in no net change in total lens osmoles. Lens water did not increase in the diabetic animals with or without cataracts. The aldose reductase inhibitor Sorbinil prevented the increase in lens sorbitol in both the 21- and 44-d streptozotocin diabetic rats; cataract formation was prevented in the 44-d diabetic animals. The lens water in untreated diabetic animals with cataracts did not differ from lens water in the Sorbinil-treated diabetic animals that did not develop cataracts. Sorbinil treatment of diabetic animals was associated with normalization of both lens sorbitol and taurine levels. Taurine has been shown to serve both as an osmoregulator and as an antioxidant. The apparent increase in lens osmolality attributed to sorbitol was counterbalanced by an equimolar reduction in taurine concentration. The reciprocal relationship between taurine and sorbitol reduces the likelihood of an osmotic mechanism for sugar cataractogenesis; the reduced lens taurine, however, may increase the risk of lens protein oxidation and subsequent cataract formation. Thus in vivo sugar cataract formation may be an oxidative process rather than an osmotic phenomenon.
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PMID:Nonosmotic diabetic cataracts. 213 28

Experimental diabetic and galactosemic animal models are widely used to study diabetes-induced complications. Galactose feeding can rapidly produce cataract, retinopathy and nephropathy; it is therefore favored over the diabetic model. Although the common feature for both models is the activation of aldose reductase, there are substantial differences between the two--not only does the rate of cataract progression differ but the metabolic patterns are far more complex than for polyol production alone. We here present the result of a comparison between diabetic and galactosemic lenses and show the differences in phosphorus and aldose metabolism, cell integrity and osmotic environment.
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PMID:Metabolic studies of galactosemic cataract. 220 47


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