Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fresh calf lesnses incubated in nutritive media containing dexamethasone phosphate or ouabain in concentrations ranging from 1 X 10(-4) M to 1 X 10(-8) M developed cortical opacification and showed significant inhibition of Na(+)-K(+) ATP'ase activity. Over a 3-day incubation period the decrease in Na+-K+ ATP'ase activity correlated well with the observed decrease in light transmission. The degree of enzyme inhibition and decrease in light transmission varied directly with the concentration of dexamethasone phosphate and ouabain, with significant changes observed at 'physiologic' and 'pharmacologic' concentrations of these agents. Lenses incubated for 4 days in dexamethasone phosphate or ouabain showed substantial increases in water content as well as an increase in Na+ and a decrease in K+ concentration. These data suggest that inhibition of the cation pump may play a significant role in the formation of steroid cataract in vitro.
 ...
PMID:In vitro production of steroid cataract in bovine lens. Part II: measurement of sodium-potassium adenosine triphosphatase activity. 23 7

In Part I1 of this study, the thermolability of lens hexokinase was implicated in the development of an experimental "hypoglycemic" cataract. After eight hours of glucose deprivation, there is a precipitous loss of lens hexokinase. This occurs approximately nine hours prior to the disorganization of the other enzymatic steps in glycolysis. Epithelial hexokinase, as an immediate response to glucose deficiency, shifts from the soluble to the insoluble phase. There is no such shift in the cortex-nucleus where only soluble hexokinase is found. After eight hours of glucose deprivation, both soluble and insoluble hexokinases throughout the lens undergo rapid deactivations. During the first eight hours of glucose deprivation the loss of lenticular ATP and K+ and the gain in wet weight can be reversed by restoring normal glucose levels; beyond eight hours the changes are irreversible. During the period of reversibility, hexokinase activity levels are normal; during the period of irreversibility hexokinase activity is 10 to 20 per cent of normal. Of the substances tested (mannose, galactose, fructose, glutamine, adenosine) only mannose could sustain the lens in the absnece of glucose. Neither endogenous free glucose nor glycogen could sustain the lens in the face of glucose deprivation. There appear to be no alternative exogenous or endogenous energy yielding substrates. The younger the animal, the more susceptible is its lens to glucose deprivation. This most certainly is a reflection of the increased susceptibility of younger lenses to osmotic stress, since lenses in each age group manifested similar changes in hexokinase activity, ATP, Na+, and K+ level.
 ...
PMID:Mechanism of "hypoglycemic" cataract formation in the rat lens. II. Further studies on the role of hexokinase instability. 93 98

Lenses from 100 gram albino rats remain clear and possess normal levels of Na+, K+, ATP, and hexokinase activity for 20 hours incubated in medium containing 12 mM glucose. Below 2.0 mM glucose, a cataract forms and there is an abrupt rise in lens Na+ and wet weight, a fall in lens K+, ATP, and hexokinase activity. The cataract is a thin lamellar opacity involving the anterior and posterior surfaces of the lens. If the lens is deprived of glucose for 48 hours, a nuclear cataract forms; the cortex between the superficial lamellar opacity and the nucleus being clear. This experimental cataract bears a striking resemblance to the hypoglycemic cataract seen in children. The thermal deactivation of hexokinase follows rapidly upon the depletion of its substrates (ATP and glucose) and is a primary factor leading to cataract formation. This was established by incubating the lens with 2-deoxyglucose, a competitive inhibitor of lens hexokinase. This compound blocks the entry of glucose into the glycolytic sequence. The cataract formed in its presence is identical morphologically and biochemically to that observed in a glucose-free medium. The effects of 2-deoxyglucose are prevented by increasing the glucose level; this rules out a direct toxic influence of 2-deoxyglucose and further supports the primary role of hexokinase thermolability in the etiology of this experimental cataract. This in vitro system appears to be an excellent experimental model for the study of the human hypoglycemic cataract.
 ...
PMID:Mechanism of "hypoglycemic" cataract formation in the rat lens. I. The role of hexokinase instability. 118 8

The effect of pyruvate on the progress of galactose cataract has been studied. Pyruvate was administered topically in the form of eye drops. Such treatment was found to delay the onset of the cataractous changes. Cataract formation was studied by visual inspection with pen light, as well as with slit lamp biomicroscopy in the intact animal. The delay in the formation of cataract was associated with the preservation of the levels of lens ATP, soluble proteins and the decreased accumulation of galactitol. In vitro organ culture experiments yielded similar results.
 ...
PMID:Prevention of galactose cataract by pyruvate. 159 5

Three newly detected dominant cataract mutations (Asc-1, Cat-3vao, Tcm) were investigated for effects on osmotic alterations in the lenses of heterozygotes. The lens wet weight was reduced in two mutant lines (Cat-3vao and Tcm), and the water content in the lenses of the Cat-3vao mice was increased. Moreover, in the cataractous lenses from Cat-3vao mice, the sodium-potassium-adenosine triphosphatase (Na(+)-K(+)-ATPase) activity was enhanced and the ATP concentration, correspondingly decreased. The osmotic variations observed in the Cat-3vao mutants might have been due to a metabolic response to the yet unknown, primary pathological event. The lenses of the other two mutant lines (Asc-1 and Tcm) revealed no alterations that could be related to osmotic stress. In no mutant line investigated could a decrease in Na(+)-K(+)-ATPase activity be demonstrated that was similar to the causative factor in the Nakano mutant line. The Cat-3vao mice exhibited some similarities to the Philly mutant line.
 ...
PMID:Osmotic state of lenses in three dominant murine cataract mutants. 216 48

The Nakano mouse is a hereditary cataract model whose most characteristic change is a deficiency in lens Na+,K(+)-ATPase. Consequently, there is a change in lenticular sodium and potassium ion levels just before cataract formation. The amounts of calcium ion also change suddenly in the lens, with accumulated levels higher than any other type of cataract. Other biochemical changes coincide with the development of lens opacity, including decreases in the levels of reduced glutathione, ATP, biosynthetic activity of proteoglycans in epithelial cells, and the permeability of gap junction channels in fiber cells. The decrease in the activity of Na+,K(+)-ATPase results in changes in a number of key metabolic parameters, resulting in the eventual opacification of the Nakano mouse lens at approximately 30 days of age.
 ...
PMID:Hereditary cataract of the Nakano mouse. 219 7

The rotational diffusion behavior of phosphorus metabolites present in calf lens cortical and nuclear homogenates was investigated by the NMR technique of 31P off-resonance rotating frame spin-lattice relaxation as a means of assessing the occurrence and extent of phosphorus metabolite-lens protein interactions. 31P NMR spectra of calf lens homogenates were obtained at 10 and 18 degrees C (below and above the cold cataract phase transition temperature, respectively) at 7.05 T. Effective rotational correlation times (tau 0,eff) for the major phosphorus metabolites present in cortical and nuclear bovine calf lens homogenates were derived from nonlinear least-squares analysis of R vs omega e (spectral intensity ratio vs precessional frequency about the effective field) data with the assumption of isotropic reorientational motion. Intramolecular dipole-dipole (1H-31P, 31P-31P), chemical shift anisotropy (CSA), and solvent (water) translational intermolecular dipole-dipole (1H-31P) relaxation contributions were assumed in the analyses. In those cases where the limiting value of the spectral intensity ratio failed to reach unity at large offset frequency, a modified formalism incorporating chemical exchange mediated saturation transfer between two sites was used. Values of tau 0,eff for phosphorus metabolites present in the cortex varied from a low of ca. 2 ns [L-alpha-glycero-phosphocholine (GPC)] to a high of 12 ns (alpha-ATP) at 10 degrees C, whereas at 18 degrees C the range was from ca. 1 to 9 ns. For the nucleus the tau 0,eff values ranged from ca. 3 ns (GPC) to 41 ns (Pi) at 10 degrees C; at 18 degrees C the corresponding values ranged from 4 to 39 ns. For PME (phosphomonoester; in lens the predominant metabolite is L-alpha-glycerol phosphate) at 18 degrees C evidence was obtained for binding and subsequent exchange with solid like protein domains. The diversity in tau 0,eff values for lenticular phosphorus metabolites is suggestive of differential binding to more slowly tumbling macromolecular species, most likely lens crystallin proteins. Corresponding measurement of tau 0,eff values for the mobile protein fraction present in calf lens cortical and nuclear homogenates at 10 and 18 degrees C, by 13C off-resonance rotating frame spin-lattice relaxation, provided average macromolecular correlation times that were assumed to represent the bound metabolite state. A fast-exchange model (on the T1 time scale), between free and bound forms, was employed in the analysis of the metabolite R vs omega e curves to yield the
 ...
PMID:Off-resonance rotating frame spin-lattice NMR relaxation studies of phosphorus metabolite rotational diffusion in bovine lens homogenates. 227 17

Intact rat lenses were incubated in riboflavin-containing Tyrode solution or medium-199, generating photochemically active species of oxygen and the oxidative stress measured in terms of the decrease in active accumulation of rubidium, and the fall in the levels of glutathione and ATP. Addition of pyruvate to the medium prevented the tissue against oxidative damage as evidenced by a greater accumulation of rubidium and higher levels of glutathione and ATP. Pyruvate was thus found to be effective against the toxicity of oxygen derivatives, particularly the hydrogen peroxide. In dark experiments also, conducted in glucose-free medium, the uptake of rubidium was substantially greater in the presence of pyruvate. The levels of ATP were also higher. These results, therefore, suggest that this ketoacid is beneficial to the tissue through its ability to decompose H2O2 as well through providing a metabolic support. The development of in vitro cataract under the photochemical effects of riboflavin and oxygen was also effectively thwarted by pyruvate. The results are thus potentially useful from the point of view of developing pyruvate and similar compounds as effective anticataract agents.
 ...
PMID:Photoinduction of cataracts in rat lens in vitro. Preventive effect of pyruvate. 237 72

The pulse Fourier NMR was employed to measure the artificial diabetic cataract lens at various stages of its formation, and the lenses of the normal rats. Data obtained by using this method show that all the peaks that of water concentrate in the range of delta less than 4 ppm. The peak value at delta = 3.20 ppm is on a marked increase during the formation of cataract which is caused by the phosphate metabolites, such as GPC, ATP, ... etc, in cataract lens. With the development of the disease, the peak width at delta = 3.73 ppm becomes greater and greater, which shows that the activity of sorbitol dehydrogenase has decreased. This leads to a high concentration of the sorbitol in the cataract lens. Consequently, the osmosis pressure in the cataract lens is increased, and excessive water might dip into the crystalline lens to keep the balance of the osmosis pressure. And this might result in the hydration of the fiber cell of the crystalline lens, which might cause a swelling or blisters. These results are in favour of the prolongation of the relaxation time of cataractous lens reported in our other papers, and also support those gained by biochemical studies issued in the medical literature.
 ...
PMID:[Detection of sorbitol content in crystalline lens of normal rats and rats with diabetic cataract by 1H-NMR]. 239 Oct 91

Cataractogenesis was studied in young rats homozygous for the radiation-induced recessive cataract mutation cat. Homozygous cat/cat rats have reduced body weight (about two-thirds of the wild type) when 3 weeks old. The litter size is also diminished to about two-thirds of the wild type. For lens-specific parameters, as compared with homozygous wild type, the wet weight of the cataractous lenses is reduced, although the concentration of water-soluble lens proteins per wet weight is the same. No major alterations could be detected in the pattern of the water-soluble lens proteins separated by isoelectric focusing or gel electrophoresis run with or without mercaptoethanol. Additionally, no statistically significant alterations could be detected in the biochemical parameters of the lens used as indicators for osmotic stress (water content of the lens and the Na+-K+-dependent ATPase), for the energy state (ATP) and for the redox state (oxidized glutathione and superoxide dismutase). In contrast, the activity of transglutaminase is significantly enhanced in lenses as well as in the liver of young cat-rats, which might be understood as a biochemical marker for alterations in the developmental program. Cataractogenesis in the cat-rat is, therefore, suggested to be part of a syndrome including dwarfism and reduced litter size.
 ...
PMID:Biochemical analysis of young rats homozygous for the cataract mutation cat. 256 75


1 2 3 4 5 6 7 8 9 Next >>