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 loss of calcium homeostasis in the lens is thought to play an important role in cataract formation. Although both lens Ca(2+)-ATPase and membrane lipid permeability are essential to calcium homeostasis, membrane permeability has been studied less extensively. In the present study, the calcium permeability of large unilamellar vesicles (LUVs) prepared from bovine lens cortical lipids has been characterized. When a calcium gradient had been established by the addition of CaCl2 to the external medium, calcium influx through the membrane was monitored by calcium concentration sensitive changes in Fura-2 fluorescence as a function of time. The calcium permeability coefficient, P, was 4.46 x 10(-13) cm s-1 at 37 degrees C. This value was about 4 fold higher than that for LUVs prepared from egg phosphatidylcholine and many times higher than that for LUVs prepared from sphingomyelin. These results provide a basis for future studies of factors that influence the permeability of lens cell membranes to calcium.
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PMID:Calcium permeability in large unilamellar vesicles prepared from bovine lens cortical lipids. 909 27

Anti-cataract activity of vitamin E analog with shortened side chain--2'-4'-methyl-pentenyl-acetoxy-2,5,7-tetramethylchroman has been studied. It is shown on the model system that the analog of vitamin E inhibits the increase of the lens agent fluorescence under irradiation of its homogenates by polychrome light. Taking no negative effect on the lens capsule epithelium, the drug normalizes the content of vitamin E in the blood and increases activity of Na+, K+, ATPase in the cortex and capsule of rabbits lenses in dynamics under simulation of light cataract in vivo.
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PMID:[Anti-cataract activity of a vitamin E analog]. 922 55

Cataract is responsible for rendering several million people blind throughout the world and is also by far the most common cause of low visual acuity. Although cataract surgery is common, routine and effective, posterior capsule opacification (PCO) occurs in 30-50% of patients following modern cataract surgery. This condition arises from stimulated cell growth within the capsular bag after surgery. The resulting decline in visual acuity requires expensive laser treatment, and PCO therefore prevents modern cataract surgery from being carried out routinely in underdeveloped countries. The present study, using a human lens capsular bag culture system, has confirmed that cells from a wide age range of donors proliferate in the absence of added serum protein and explains why PCO is such a common problem even in aged patients. This study also provides one possible solution for PCO by using polymethylmethacrylate (PMMA) implanted intraocular lenses as a drug delivery system. PMMA lenses coated with thapsigargin, a hydrophobic inhibitor of endoplasmic reticulum (ER) (Ca2+)-ATPase, greatly reduced cell growth in the capsular bag at relatively low coating concentrations (200 nM) but, more significantly, induced total cell death of the residual anterior epithelial cells at higher concentrations (>2 microM).
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PMID:Thapsigargin-coated intraocular lenses inhibit human lens cell growth. 928 18

FK506 (tacrolimus), a potent immunosuppressant, is used for inhibiting allograft rejection in the organ transplantation field. In a preclinical toxicity study in rats, FK506 induced various toxicities, including renal and pancreatic injuries. One of these toxic findings was cataract, and we have found that cataract appeared in rats dosed orally with FK506 for 13 weeks and more. Therefore, to better elucidate the onset mechanism of FK506-induced cataract, we measured biochemical parameters, such as sorbitol, Na,K-ATPase and glutathione in the lens of rats. Rats were dosed with FK506 in oral daily doses of 0.2, 1 or 5 mg/kg for 13 weeks, the lowest dose of which approximated the expected clinical dosage. Cataract developed in the 5-mg/kg/day group, with an incidence of 25%, whereas no cataract formation was observed in the 0.2- or 1-mg/kg/day groups. Five mg/kg/day led an increase of sorbitol and a decrease of reduced type glutathione, but did not affect Na,K-ATPase activity of the lens. FK506 is known to have diabetogenicity mediated through pancreatic injury, which appears as vacuolation of islet cell in rats. Five mg/kg/day of FK506 induced an elevation of blood glucose associated with glucose intolerance, and decrease of both basal insulin level and insulin content in the pancreas, and the changes were in parallel with the cataract development in the present study. On the other hand, diabetic parameters did not change in the 0.2- or 1-mg/kg/day groups. These observation suggest that diabetes developed in the rats dosed with 5 mg/kg/day of FK506. Coadministration of a novel aldose reductase inhibitor, Zenarestat, at an oral dose of 50 mg/kg/day resulted in a reduction of incidence of the FK506-induced cataract and a decrease of sorbitol levels in the lens when compared to that in the lens of rats dosed with 5 mg/kg/day of FK506. These results suggest that FK506-induced cataract in rats is due to an accumulation of sorbitol in the lens, secondary to the diabetogenic effect of FK506. FK506 treatment at the doses of 0.2 and 1 mg/kg/day neither affected parameters indicative of diabetes nor induced cataract in rats, suggesting that the cataract would not develop with FK506 if diabetic parameters were kept under control.
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PMID:Cataract development induced by repeated oral dosing with FK506 (tacrolimus) in adult rats. 935 35

The preventive action of vitamin E (Vit. E)-containing liposomes on cataractogenesis was examined in male Wistar rats (five weeks old) fed a 25% galactose diet. Vit. E-containing liposomes prepared with dipalmitoylphosphatidylcholine were instilled into both eyes three times a day over a 45-day period. Cataract appeared at 18-day galactose feeding and developed gradually thereafter. Simultaneous Vit. E-containing liposome instillation delayed this cataractogenesis. Lenses of 18-day galactose-fed rats showed decreases in Vit. E and reduced glutathione (GSH) contents and Na+, K(+)-ATPase activity and increases in lipid peroxide (LPO), galactitol, and water contents. Lenses of 45-day galactose fed rats showed decreases in GSH content and Na+,K(+)-ATPase activity and increases in Vit. E, LPO, galactitol, and water contents. Serum Vit. E and cholesterol levels decreased in 18-day galactose-fed rats, while both levels increased in 45-day galactose-fed rats. Simultaneous Vit. E-containing liposome instillation prevented these changes except for the changes of lenticular galactitol and water contents and serum Vit. E and cholesterol levels. These results indicate that simultaneously instilled Vit. E-containing liposomes can delay cataractogenesis in young adult rats fed a 25% galactose diet mainly by the antioxidative action of Vit. E contained in the instilled liposomes.
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PMID:Preventive action of vitamin E-containing liposomes on cataractogenesis in young adult rats fed a 25% galactose diet. 943 57

The activity of Na+,K+ATPase, gamma-glutamyltranspeptidase, ceruloplasmin, total antioxidative activity of water-soluble antioxidants, the contents of vitamins C and E, free amino-nitrogen and peroxide resistance of erythrocytes were determined at the blood's plasma of healthy persons (120 persons) and suffered from aged cataract (437 persons) of three aged groups (up to 40 years, 40-60 years and elder then 60 years). We have shown, that changes, which has been connected with cataractogenesis and age dependent changes are not equal. The lowering of activity of Na+,K(+)-ATPase, gamma-glutamyltranspeptidase and level of vitamin E was expressed less during the ageing, then during the development of lenses opacification. The increase of activity of oxidase during the cataractogenesis is less significant, then age depended inhibition of this enzyme. The opposite tendency (the lowering of activity at the patients with cataract is more expressed, then compensatory activations of these parameters at the persons of the corresponding age with transparent lenses) was revealed for total antioxidative activity of water-soluble antioxidants.
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PMID:[Biochemical blood parameters in people with a normal crystalline lens and in cataracts]. 1044 69

The effects of lysophosphatidic acid (LPA), a bioactive phospholipid, on the response of the cytosolic free Ca2+ concentration ([Ca2+]i) to hypotonic stress were studied in cultured bovine lens epithelial cells, to test whether LPA affects cellular swelling-mediated increase in [Ca2+]i, which may relate to formation of sugar cataracts. Exposure of the cells to a 30% hypotonic stress caused only a slight increase in [Ca2+]i. Pretreatment with LPA (10 microM) significantly augmented the hypotonic stress-induced [Ca2+]i response, whereas addition of LPA to the cells did not affect [Ca2+]i. The hypotonic stress-induced increase in [Ca2+]i in the presence of LPA was inhibited by Gd3+, a blocker of mechanosensitive cation channels, but not by nicardipine, a L-type Ca2+ channel blocker, or thapsigargin, an inhibitor of endoplasmic reticulum-ATPase pump. These results show that LPA sensitizes the response to hypotonic stress via increase in Ca2+ influx through Gd3+-sensitive stretch-activated ion channels, and not via Ca2+ release from intracellular stores. On the other hand, LPA did not affect the [Ca2+]i response to ATP, a Ca2+ mobilizing agonist. Therefore, LPA sensitizes the hypotonic stress-induced [Ca2+]i response in lens epithelial cells, suggesting that LPA potentiates the development of cataracts induced by cellular swelling such as sugar cataract.
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PMID:Sensitizing effect of lysophosphatidic acid on Ca2+ response to hypotonic stress in cultured lens epithelial cells. 1044 15

Lens lipid composition and lipid hydrocarbon chain structure change with age, region and cataract. Since the lens Ca(2+)-ATPase pump is important to the maintenance of calcium homeostasis and lens clarity, muscle sarcoplasmic reticulum Ca(2+)-ATPase was reconstituted with bovine lens lipids and dihydrosphingomyelin, the rare and major phospholipid of the human lens. Ca(2+)-ATPase activity was found to be about 5 times lower when the pump was reconstituted into dihydrosphingomyelin or lens lipids compared to native sarcoplasmic reticulum lipids. The addition of cholesterol to levels ranging from 13-53 mole%, had no affect on reconstituted Ca(2+)-ATPase activity. Ca(2+)-ATPase activity correlated with the degree of hydrocarbon chain saturation. The greater levels of saturation are a consequence of the high sphingolipid content in the reconstituted systems. These data support the hypothesis that changes in lens lipid composition or structure could affect Ca(2+)-ATPase activity in human lenses. Because the mechanisms governing Ca(2+)-ATPase activity in vivo are much more complex than in these simple reconstituted systems, this study represents an initial step in the elucidation of the relationships of endogenous membrane lipid composition-structure and function.
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PMID:Ca(2+)-ATPase activity and lens lipid composition in reconstituted systems. 1047 40

Sodium-potassium-adenosine triphosphatase (Na,K-ATPase) has long been recognized for its role in regulating electrolyte concentrations in the lens, within which the electrolyte balance is vital to lens transparency. In this study, we compared the abundance of the alpha-subunit of Na,K-ATPase in lens epithelia of patients with senile cataracts, in order to examine the role of this enzyme in various types of lens opacity. Human lens epithelia were collected from 27 patients with senile cataracts who had undergone phacoemulsification. The type and the severity of lens opacity were graded and scored according to the Lens Opacities Classification System II. The mean age of the patients was 67.5 years (range, 46-80 yr). Abundance of the Na,K-ATPase alpha-subunit peptide in the lens epithelium was quantified by means of Western immunoblotting. Immunoblotting revealed that the amount of Na,K-ATPase alpha-subunit tended to decrease with increased cataract severity. In hypermature cataracts, the Na,K-ATPase alpha-subunit was barely detectable. The amount of alpha-subunit of Na,K-ATPase was inversely correlated with the overall severity of cataract (r = -0.64, p = 0.002). However, the inverse correlation was significant only in the cortical region (p = 0.027). As the cortex is located adjacent to the lens epithelium, it is directly affected by the loss of function of Na,K-ATPase in the epithelium. Such loss could result in water accumulation, vesicles, water clefts, Morgagnian globule formation, and Morgagnian cataract.
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PMID:Na,K-ATPase in lens epithelia from patients with senile cataracts. 1056 Feb 39

Both hypertension and cataract formation have been associated with reductions in sodium pump activity, possibly as a result of an endogenous inhibitor. The objective of the present study was to answer 4 closely related questions: (1) Is the lens sodium pump effectively inhibited by a labile, digitalis-like factor we have identified in the peritoneal dialysate from hypertensive patients in end-stage renal failure? (2) How does that inhibition compare to that induced by ouabain? (3) Does sodium pump isoform distribution determine the degree of lens sodium pump inhibition? (This question was precipitated by the unanticipated finding that the labile DLF was more effective in inhibiting lens sodium pump than was anticipated.) (4) Is sodium pump activity altered in lens in response to increased salt intake, a maneuver known to increase endogenous digitalis-like factor? We found that whereas ouabain produced equivalent or significantly less inhibition of lens Na(+), K(+)-ATPase from calf or rabbit, respectively, compared with brain, labile digitalis-like factor preferentially inhibited lens compared with brain. Analysis of whole-lens preparations from rabbit, calf, and normal human lens revealed substantial alpha2- and alpha3-isoforms of the sodium pump but little alpha1-isoform. Ouabain inhibition of whole-lens Na(+),K(+)-ATPase from rabbit and calf were comparable: for rabbit lens, K(i)=5.2x10(-7) mol/L; for calf lens, K(i)=1.0x10(-6) mol/L. Limited quantities of labile digitalis-like factor prohibited similar determinations; however, its concentration-activity profile paralleled that of ouabain. Na(+), K(+)-ATPase activity, measured in the 3 major anatomic regions of lens and normalized to nucleus, was greatest in epithelium (56. 9+/-17.9) compared with cortex (5.8+/-1.4) and nucleus (1.0+/-0.0; P=0.01). Immunohistochemistry of rabbit lens found abundant alpha2- and alpha3-isoforms in epithelium and limited alpha3 but undetectable alpha1 in cortex and nucleus. Finally, rats randomized to a high Na diet showed significantly reduced lens Na(+), K(+)-ATPase activity compared with those on a low Na diet, consistent with the effects of a sodium pump inhibitor. In conclusion, the present study suggests that digitalis-like factor may provide a link between hypertension and cataract formation.
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PMID:Sodium pump inhibition and regional expression of sodium pump alpha-isoforms in lens. 1056


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