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)

The reductone ascorbic acid, present in the crystalline lens in concentrations higher than those of glucose, is capable of undergoing nonenzymatic "browning" in the presence of lenticular proteins. We studied the nonenzymatic browning with ascorbate in model systems employing bovine serum albumin and lens crystallins. When bovine serum albumin, alpha-crystallin, or gamma-crystallin was incubated with [14C]ascorbic acid, the formation of yellow and then brown condensation products appeared to correlate with increasing protein-associated radioactivity. The fluorescence spectrum of these products was similar to that of homogenates of human cataractous lenses. We suggest that the nonenzymatic reaction of lens crystallins with ascorbic acid may contribute, at least in part, to the color changes of aging lenses and to the physical lenticular deterioration leading to senile cataract. High dietary intake of ascorbic acid did not affect the fluorescence spectrum of murine lenses; thus, we assume that the speed and extent of the lenticular browning reactions must depend on a deterioration of other factors of the multicomponent antioxidant system of the eye.
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PMID:The role of ascorbic acid in senile cataract. 386 54

The incidence of visually disabling cataract was estimated by the rate of first cataract extraction in a population of Pima Indians in Arizona. The annual age-specific rates of cataract surgery (first and second eyes) were 3.7 to 5.9 times as high as the estimated US rates. Diabetes was a strong risk factor for first cataract surgery in all age and sex groups except in men aged 75 to 84 years. Overall, with age and sex controlled, the rate of first cataract surgery was 2.2 times as high (95% confidence interval, 1.3 to 3.9) in diabetic as in nondiabetic subjects. Cataract surgery was related to the duration and type of treatment of diabetes. Insulin-treated diabetics had about five times the rate of those with normal glucose tolerance. The rate of cataract surgery was lowest in subjects with normal glucose tolerance, somewhat higher in those with impaired glucose tolerance, and even higher with increasing duration of diabetes.
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PMID:Incidence of cataract extraction in Pima Indians. Diabetes as a risk factor. 388 67

Data on the clinical features of the Werner syndrome in 102 patients in Japan were collected by sending questionnaires to major hospitals and analyzed. The male-to-female ratio was 3 to 2 and the incidences of consanguinity and familial occurrence were 51% and 39.4%, respectively. These patients were divided into 3 subgroups; group 1, 2, and 3 lacked short stature, cataract, and hypogonadism, respectively. Each group had somewhat different clinical features. Endocrine and metabolic abnormalities in the Werner syndrome patients were compared with those in normal aged subjects. Impaired plasma growth-hormone responses to insulin and arginine were more common and impaired plasma thyrotropin responses to TRH were less common in the Werner syndrome patients than in aged subjects. Plasma LH and FSH levels were higher in most patients than those in age- and sex-matched controls; also, their serum testosterone concentrations were lower than those in age-matched controls and testicular biopsy revealed more marked atrophy than in aged subjects. Serum triiodothyronine levels tended to be lower than in age-matched controls. Oral glucose tolerance test revealed diabetic glucose tolerance in 55% and impaired glucose tolerance in 22%, although fasting blood glucose levels were elevated only in 20%. Plasma insulin response to glucose was more exaggerated in those with the Werner syndrome than in normal aged subjects. The euglycemic glucose clamp method revealed lower glucose disposal rates and insulin sensitivity indices in the Werner syndrome than in normal subjects of similar age. The number of erythrocyte insulin-binding sites was normal in the Werner syndrome patients. These results suggest a postreceptor defect in insulin resistance in the Werner syndrome.
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PMID:Clinical, endocrine and metabolic aspects of the Werner syndrome compared with those of normal aging. 390 66

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

The rapid conversion of glucose to sorbitol by aldose reductase and the consequent hyperosmolarity of the cytoplasm has been shown to be the primary cause of the so-called "sugar" or "osmotic" cataract in many animal lenses. It is not as clear, however, that hyperosmolarity is the principal factor in the etiology of cataracts in human diabetic subjects. In fact, the comparatively low activity of aldose reductase in the human lens as compared with several animal lenses, and the osmotically insignificant levels of sorbitol pathway products (sorbitol and fructose), suggest that hyperosmolarity, per se, may not be as important a factor in human cataract formation as it is in animals. We present evidence that the flux of glucose and sorbitol through the rat lens is markedly reduced by oxidative stress (0.1 mM H2O2). Sorbitol accumulation is reduced by 114%, sorbitol turnover is reduced by 78%, sorbitol production is reduced by 90%, fructose accumulation is reduced by 60%, and fructose turnover is reduced by 76% in the presence of 36 mM glucose. H2O2 does not affect glucose turnover, the glucose rate constant, or the ATP level significantly at 36 mM glucose, but at 5.5 mM glucose, 0.2 mM H2O2 leads to a rapid loss of ATP that can be prevented by 0.04 mM sorbinil, an aldose reductase inhibitor. These results suggest that inhibition of aldose reductase by sorbinil renders rat lenses better able to cope with oxidative stress. In the absence of an aldose reductase inhibitor, elevating ambient glucose may render a lens less able to scavenge oxidants by diverting NADPH into sorbitol production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of oxidation on sorbitol pathway kinetics. 395 80

The possibility that vitamin E or other antioxidants might prevent cataracts was tested by incubating rat lenses in vitro in galactose-enriched medium or by treating rats fed a diet containing 50% galactose (w/w). The vitamin E was added to the medium at 2.4 microM, and to the diet at a level of 5 g kg-1 diet. In vitro, lenses incubated with 55.6 mM galactose underwent globular degeneration, which was partially prevented by addition of vitamin E (2.4 microM). Even in such vitamin E-protected lenses, which appeared clear, many small globules could be seen in the region of interdigitation at the 'corners' where hexagonal cells intersected. In vivo, in dietary experiments, a dense nuclear opacity of the lens was observed after approximately 5 weeks; unlike diabetic cataracts, this was not prevented by the addition of vitamin E to the diet. The extensive globular degeneration observed was typical of that found in long-term (21-week diabetic) cataracts. Although no significant difference in cataract incidence was observed, the extent of damage in vitamin E-treated rat lenses appeared to be less. The difference in effectiveness of vitamin E in galactose-induced cataracts, as compared to diabetic cataracts, is tentatively ascribed to (1) the more severe osmotic stress expected from the products of the aldose reductase pathway for galactose and (2) the greater depletion of reduced pyridine nucleotides (NADPH + NADH) expected of galactose as compared to glucose.
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PMID:Modelling cortical cataractogenesis VII: Effects of vitamin E treatment on galactose-induced cataracts. 397 62

In a patient having brittle, juvenile-onset diabetes, transient monocular visual loss occurred repeatedly whenever there were wide fluctuations in serum glucose. Amaurosis fugax was suspected. The visual loss differed, however, in that it persisted over a period of hours to several days. Direct observation eventually revealed that the relatively sudden change in vision of one eye was associated with opacification of the lens and was not accompanied by an afferent pupillary defect. Presumably, a hyperosmotic gradient had developed with the accumulation of glucose and sorbitol within the lens. Water was drawn inward, altering the composition of the lens fibers and thereby lowering the refractive index, forming a reversible cataract. Hypoglycemia is also hypothesized to have played a role in the formation of a higher osmotic gradient. The unilaterality of the cataract is attributed to variation in the permeability of asymmetric posterior subcapsular cataracts.
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PMID:Reversible monocular cataract simulating amaurosis fugax. 403 3

During the last 10-15 years, investigations into the biology and biochemistry of the lens have demonstrated that the age changes observed cannot be the only cause of the formation of senile cataract. The various types of opacities and the wide age range in which they begin indicate a multifactorial origin involving endogenous and exogenous risk factors. Initial epidemiological studies have identified certain risk factors. Experimental cataract research is able to elucidate possible damaging mechanisms by using cataract models, for instance, the cataracts caused by excess carbohydrate (galactose, glucose), naphthalene application, ionizing rays, or by additional cocataractogenics, thus indicating steps for countermeasures. Taking (true) diabetic cataract of rats after Streptozotocin injection as an example, the efficacy of aldose reductase inhibitors is shown. Even if additional cataractogenic factors such as naphthalene and X-rays are applied, diabetic lens opacities can be prevented completely. Damage by naphthalene is due to an increased oxidative change in the lens protein. Several substances promoting the antioxidative capacity of the lens, thereby inhibiting cataract formation, are already available. Preclinical or clinical studies have demonstrated the efficacy of only a few of the commercially available anticataract drugs. The results of animal experiments presented here may well represent a basis for the development of really effective anticataract drugs.
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PMID:[What possibilities exist to modify cataract development on the basis of current biochemical knowledge? Where can drugs act?]. 404 54

Calcium has long been known to play a role in cataract formation but techniques have only recently become available for investigating the physiological mechanisms. Previous studies showed that lens membrane permeability alters when the external calcium concentration falls below 1 mM, so it was interesting that values for human aqueous from cataract patients ranged from 0.45 to 2.0 mM. The mean value for the aqueous was one half that for the plasma. The calcium concentration in cataractous lenses ranged from 0.1 to 64 mM and lenses with a high calcium concentration also had a high sodium content. In lenses with near normal sodium content the highest calcium concentrations were associated with highly localized opacities, while nuclear cataracts had a low calcium content. The relationship between calcium and transparency was investigated in a rat lens system using ion-sensitive microelectrodes. The distribution of free calcium in the lens varied with age and was correlated with a change in the sensitivity of the lens to cold cataract and a change in lens birefringence. The highest free calcium levels were obtained from lenses incubated in 10 mM-calcium in the absence of glucose and these lenses showed most light scattering. Ion-sensitive microelectrode techniques applied to human lenses yielded calcium levels of 0.1 microM-2 mM. In lenses with dense, highly localized opacities the calcium distribution was not uniform and was highest in regions that scattered most light. The movement of calcium through individual membrane channels was investigated using patch clamp techniques. Three types of ionic channels have been identified in the lens. The smallest appears to be a calcium channel; the larger current fluctuations are associated with sodium and potassium movements. In organ culture studies of the bovine lens, a marked decrease in protein synthesis and net leakage of proteins was associated more strongly with an increase in calcium than with an increase in sodium. The stability of the lens protein gel thus seems to depend on maintaining a low internal level of calcium ions.
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PMID:Calcium and the physiology of cataract. 609 95

22% of a group of adult Neapolitans were found to have persistent high lactase activity, and 16% were lactose absorbers as indicated by measurement of breath hydrogen concentration and rise in blood glucose after oral lactose administration. Among adults in the same area with idiopathic senile or presenile cataract 49% were identified as lactose absorbers with the breath hydrogen test and 55% by the rise in blood glucose. These results suggest that adults able to absorb galactose from a lactose-containing diet are especially susceptible to senile or presenile cataract.
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PMID:High frequency of lactose absorbers among adults with idiopathic senile and presenile cataract in a population with a high prevalence of primary adult lactose malabsorption. 614 22


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