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)

Previous studies have indicated that in vivo exposure to hyperbaric O2 may be associated with the development of nuclear cataract. In the present work, in vitro effects of hyperbaric O2 on rabbit lenses were investigated following culture of the lenses in an atmosphere of 99% O2 at pressures ranging between 1 and 100 atm. Treatment with O2 resulted in a significant decrease in the level of reduced glutathione (GSH) in the lenses even at the lower pressures studied (less than 8 atm). At 100 atm O2 the loss of GSH was 85% after a 3 hr exposure. At 8 atm O2 a significant drop in GSH concentration was shown to occur in the lens nucleus prior to loss of the tripeptide in the superficial cortex. O2-treated lenses became hazy in appearance, especially at the higher pressures, but did not become densely opaque. Pressures of N2 up to 100 atm had no effect on either lens transparency or on the concentration of GSH. Although oxidized glutathione (GSSG) was detected in the whole lens at pressures of O2 as low as 4 atm, no change in GSH level or evidence for GSSG accumulation was observed in the capsule-epithelium of the lens at pressures as high as 50 atm O2. Ninety percent of the GSSG present in lenses after exposure to 100 atm O2 could be reconverted to GSH by subsequent culture of the lenses under normal conditions. Exposure of lenses to 50 atm O2 produced a three-fold stimulation of hexose monophosphate shunt activity, equal to that which has been reported for treatment of lenses with 0.06 mM H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exposure of rabbit lens to hyperbaric oxygen in vitro: regional effects on GSH level. 341 15

Abnormalities in glucose metabolism are thought to be among the main causes of cataract formation. The authors have made noninvasive biochemical measurements of the lens that provide information concerning glucose metabolism in the lens epithelium. The autofluorescence of reduced pyridine nucleotides (PN) and oxidized flavoproteins (Fp) within the rabbit lens were noninvasively measured as a function of depth using redox fluorometry. The peak of the autofluorescence at 440 nm (excited at 360 nm) and 540 nm (excited at 460 nm) were determined at the lens epithelium. When 8 mM sodium pentobarbital, a known inhibitor of mitochondrial respiration, was applied to the lens, the autofluorescence peak at 440 nm increased and that at 540 nm decreased. The 440 nm autofluorescence is thought to be from reduced pyridine nucleotides, whereas the 540 nm autofluorescence is from the oxidized flavoprotein. Blocking lens respiration with pentobarbital caused an increase in the PN/Fp ratio by a factor of 3 within 3.5 hr after pentobarbital application.
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PMID:Noninvasive measurements of pyridine nucleotide and flavoprotein in the lens. 357 Jun 89

This study was designed to document and quantify changes in lens clarity over 24 months in a group of diabetic patients. One hundred thirty-four type I and type II diabetics of 3 months' to 45 years' duration with an average age of 53.5 +/- 7 years volunteered to participate in this prospective study. Patients were evaluated upon entry and at 6-month intervals. Scheimpflug lens photographs (Topcon SL45) were taken at each visit. All photographs were evaluated by densitometry which allowed quantification of the light scattering in the various lens layers. A significant and progressive (4-7% every 6 months) increase in light scattering was observed in the lens anterior superficial lens cortex over 24 months. The rate of change in lens clarity was similar in all patients regardless of the clinically observable lens change type (nuclear, cortical, posterior subcapsular, or mixed). Patients who were younger at enrollment, having diabetes of shorter duration and higher glycosylated hemoglobin values (a measure of long-term glucose control), were identified to be at greater risk of having increased densitometry values in the anterior superficial lens cortex. Only a few patients had significant changes in visual acuity during 24 months, and the correlation of superficial cortical lens clarity changes to clinical cataract formation and visual impairment remains to be established.
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PMID:Long-term follow-up of lens changes with Scheimpflug photography in diabetics. 365 55

There is good evidence that the non-enzymic chemical modification of proteins plays a role in the aetiology of cataract and diabetic sequelae. This paper presents new evidence that glycosylation of two major lens structural crystallins, alpha- and gamma-crystallins, by glucose 6-phosphate (G6P) induces conformational changes in the proteins. In addition the surface charge on the molecules is altered. These changes would affect protein-protein and protein-water interactions within the lens and could lead to disruption of the short-range order of the lens proteins which is essential for lens transparency. Conformational changes to lens proteins are known to occur in human cataractous lenses but their cause in vivo is not established. Cumulative chemical modification of proteins, over a period of decades, is a strong candidate as a causal agent.
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PMID:Conformational changes induced in lens alpha- and gamma-crystallins by modification with glucose 6-phosphate. Implications for cataract. 368 29

To determine the possible role of glucose and lipid metabolism in the formation of cataract in elderly people we studied 463 patients undergoing cataract extraction. Of 188 males, 35 (19%) had posterior subcapsular cataract (group 1), 27 (14%) had cortical cataract (group 2), and 24 (13%) had nuclear cataract (group 3). Of 275 females, 27 (10%) belonged to group 1, 44 (16%) to group 2, and 33 (12%) to group 3. Patients in group 1 were significantly younger than those of group 2 and 3. In addition, patients in group 1 had higher concentrations of fasting serum triglycerides than patients of group 2 or 3. No difference in mean concentrations of serum cholesterol was observed between the different groups. However, fasting plasma glucose concentrations were higher in group 1 patients than in those of group 2 or 3. Patients in group 1 had a higher 'Broca index' than those in group 2 or 3, with the exception of males in group 3. These results suggest that the association of hypertriglyceridemia, hyperglycemia and obesity favors the formation of a specific morphologic type of lens opacity, posterior subcapsular cataract, occurring at an early age. They imply the possibility of effective modes of preventive therapy for a subgroup of patients with 'senile' cataract.
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PMID:Identification of metabolic risk factors for posterior subcapsular cataract. 373 11

Metabolism in human senile cataracts has been studied using uniformly labeled [14C]glucose. Intracapsularly extracted lenses were cultured in TC-199 media with a glucose concentration of 5.5 mM. Results show that lactate production accounts for 97% of the glucose metabolized. Under these standard incubation conditions there is negligible accumulation of alpha-glycerol phosphate, glucose-6-phosphate, and sorbitol. The rate of lactate production was found to be relatively uniform over a range of cataract severities which were determined from the CCRG classification. The effects of several perturbants in the medium were measured. An ATP concentration of 3 mM was found to inhibit lactate production. Labeled glucose-6-phosphate in the medium was found to produce lactate at a rate approximately one half that of glucose. Elevated glucose concentration resulted in a slight decrease in lactate production and, in some lenses, production of a small amount of sorbitol. Overall, the glycolytic pathway appears to be functioning normally and without regard for cortical and nuclear opacification.
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PMID:Glucose metabolism by human cataracts in culture. 375 23

Polyhydric alcohols (polyols) are widely distributed in nature, and the enzymes of the polyol pathway (aldose reductase and sorbitol dehydrogenase) are present in many mammalian tissues. The function of this pathway remains a mystery. A primary role for the pathway in the pathogenesis of 'sugar cataract' was provided by a number of experimental observations and in the 1960s the 'osmotic hypothesis' was propounded. This hypothesis also had implications for the pathogenesis of diabetic neuropathy. However, in the 1970s doubts were raised about the validity of the hypothesis, culminating in experiments which suggested that abnormalities in myo-inositol metabolism in nerve and lens were more closely related to the glucose-induced functional changes in these tissues than was the polyol pathway. Nevertheless, increased activity of the polyol pathway must still be regarded as an instigator of the biochemical abnormalities that lead to damage of lens and nerve in diabetes mellitus.
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PMID:The polyol pathway. A historical review. 379 30

When 15-day-old developing chick embryos were administered hydrocortisone hemisuccinate sodium (HC; 0.25 mumol/egg), the content of glucose in the lens markedly increased from around 6 hr, and reached about 25-30-fold above the matched control at 24-48 hr. Thereafter, the glucose level declined and returned to the control level by 100 hr. The profile of lenticular glucose levels was similar to that of the appearance and disappearance of lens opacification. Prednisolone, as well as HC, produced cataract and the elevation of glucose in the lenses. Cortexolone and cortisone, which have weak or negligible glucocorticoid activity in developing chick embryo, could neither produce cataract nor the elevation of glucose in the lenses. An attempt was made to find similarity between this glucocorticoid-induced cataract and sugar cataract known in mammals. In both control and HC-induced cataract (stage IV-V) obtained 48 hr after HC administration, sorbitol, fructose, and glycosylation of protein could not be detected. Dehydration was observed in HC-induced cataractous lens. These data demonstrate that the glycosylation of lenticular protein and the accumulation of polyol were not involved in glucocorticoid-induced cataract formation in developing chick embryos. These results suggest a relationship between the elevation of glucose and cataract formation. However, when cataract formation was blocked by ascorbic acid treatment, the glucose level remained high. Therefore, any relationship between glucose level and cataract may be complex or indirect.
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PMID:Analysis of glucose levels during glucocorticoid-induced cataract formation in chick embryos. 380 47

Heretofore, the intracellular accumulation of sorbitol has been associated exclusively with deleterious (cataractogenic) changes in the lens. This study demonstrates a beneficial role for the sorbitol pathway in the rabbit lens, namely that of counteracting extracellular, glucose-derived, osmotic stress with the intracellular production of osmotically active sorbitol. Large and sudden increases in the extracellular glucose concentration lead to dehydration of the lens, a response that can be diminished by intracellular sorbitol and fructose production. These results are discussed in light of the impact (beneficial/detrimental) of aldose reductase inhibitors on the lens. Sugar cataract formation appears to result from continuous, rather than cyclical, activity of a pathway which normally may have a protective function in the lens.
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PMID:Sorbitol production in the lens: a means of counteracting glucose-derived osmotic stress. 380 97

Addition of pyrroline-5-carboxylate (P5C) or its precursors to rat lenses cultured for 24 hr in TC-199 medium containing 14C-glucose results in an apparent concentration-dependent increase in hexose monophosphate-pentose (HMP) pathway activity. Addition of proline, the reduction product of P5C, did not result in an increase, suggesting that stimulation of the HMP pathway is related to the reduction of P5C to proline by the enzyme P5C reductase. No apparent feedback inhibition on P5C reductase was observed. Stimulation of HMP pathway activity by P5C was also observed in the lenses of Philly and Nakano mouse, two models of congenital osmotic cataracts. Compared with its genetic control, the Swiss--Webster mouse, generally no difference in the lenticular levels of HMP pathway activity was observed in the Philly mouse--even after the onset of cataract. Stimulation of the HMP pathway in the Philly lens by P5C, however, was consistently lower than its control. In the lenses from the Nakano mouse and its genetic control, the Balb/c mouse, no difference in the percentage stimulation of the HMP pathway resulting from the addition of P5C was observed, but HMP pathway activity in the Nakano lens was consistently lower than that of the control.
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PMID:Stimulation of the hexose monophosphate pathway by pyrroline-5-carboxylate reductase in the lens. 384 59


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