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 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
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PMID:Off-resonance rotating frame spin-lattice NMR relaxation studies of phosphorus metabolite rotational diffusion in bovine lens homogenates. 227 17

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

In the bovine lens the gamma IV-crystallin fraction is a principal determinant of the phase separation and opacification temperature, Tc (Siezen et al, Proc. Natl. Acad. Sci. USA 82, 1985, 1701). We have now measured the effect on Tc of purified gamma IV-crystallin solutions produced by a variety of reagents which affect protein-protein, protein-water and water-water interactions. Ionic strengths less than physiological increase Tc dramatically, while higher ionic strength has very little effect. Calcium ion concentrations up to 8 mM produce no change in Tc. Glycerol and acrylamide both depress Tc linearly with reagent concentrations; Tc depression of gamma IV-crystallin by these compounds is quantitatively the same as for whole lens. Sulfhydryl reducing agents such as glutathione and dithiothreitol lower Tc, while hydrogen peroxide increases Tc. Changes in opacification temperature of gamma IV-crystallin produced by oxidizing and reducing agents are time-dependent and highly non-linear with reagent concentration. Our results clearly show that bovine gamma IV-crystallin is an important target protein for various reagents which are known perturbants of the opacification temperature of whole lens. The relevance of these findings to human diabetic and senile cataract formation is discussed.
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PMID:Controlled modulation of the phase separation and opacification temperature of purified bovine gamma IV-crystallin. 406 30

Cholesterol is the major lipid component of the ocular lens. The source of lens cholesterol during the first month of post-natal life of the rat was investigated by use of U18666A, a potent inhibitor of cholesterol biosynthesis which can also produce cataracts. Lenses from rats treated with U18666A at a level known to produce cataracts were of smaller size and accumulated total sterol at about one-half the rate of untreated controls. The lens content of phospholipid also lagged behind that of controls. Desmosterol accounted for 50-75% of the total sterol in lens of all treated rats, this paralleled the percent content of desmosterol in liver and serum of these animals. Lenses taken from 20-day-old treated rats and incubated in vitro synthesized little digitonide-precipitable sterol (DPS) from 3H2O as compared to lenses from age-matched controls. The steady state concentration of U18666A in lens was found to be 1-2 X 10(-6) M; this concentration almost completely blocked sterol synthesis in vitro when added to normal lenses. Although U18666A inhibited lens synthesis in vitro of phospholipids from 1,3-[3H]-glycerol and 32Pi, it did so only at levels much higher than those encountered in vivo. Thus, the changes seen in lens phospholipids appear secondary to the decreases in sterols. Since lenses of treated rats synthesized little if any sterol but accumulated sterol at one-half the rate of control lens, we conclude that during early post-natal development of the rat the ocular lens possesses the potential to satisfy about one-half of its sterol requirements from sources outside of the lens, perhaps from lipoproteins in aqueous humor. This conclusion is consistent with our earlier work which indicated that the rat's lens can furnish 50-100% of its total cholesterol by synthesis de novo during the first two weeks of life and less thereafter. The relationship of the inhibition of sterol synthesis to production of the U18666A-induced cataract is discussed.
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PMID:Source of cholesterol for the ocular lens, studied with U18666A: a cataract-producing inhibitor of lipid metabolism. 687 3

Dynamic changes in lens organophosphate metabolites during 24 hr incubation in 30 mM galactose media were measured with phosphorus-31 nuclear magnetic resonance spectroscopy. The following phosphates were quantitated from the intact crystalline lens: adenosine triphosphate (ATP), adenosine diphosphate (ADP), inorganic orthophosphate, alpha-glycerophosphate, phosphorylated hexoses and trioses, nicotinamide adenine dinucleotide, uridine diphosphoglucose and uridine diphosphogalactose, glycerol-3-phosphorylethanolamine and 3-phosphorylcholine, and an unidentified phosphorus-containing molecule. The temporal sequences of metabolic events that define the dynamic rates of accumulation or depletion of lens organophosphates reveal that the first event in the decline of the tissue upon galactose incubation is a net consumption of ATP, which occurs as a sigmoidal function with time and which is typified by a characteristic half-life of 18 hr. Alpha-glycerophosphate accumulated at an increasing rate with time, whereas ADP, inorganic orthophosphate, and the other organophosphates were essentially unchanged. Cataract formation in the subcapsular and superficial cortical regions was visible after 16 hr incubation in the experimental buffer. These findings support the hypothesis that alterations in the organophosphate levels of the lens are contributing factors to the initial formation of the experimental galactose cataract.
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PMID:Dynamic changes in the organophosphate profile of the experimental galactose-induced cataract. 707 7

A prospective study of 267 intracapsular cataract extractions was conducted to assesses what makes an eye soft and capable of safely receiving an intraocular lens implant. The study showed that the use of glycerol, given orally before the operation, plus retrobulbar anesthesia is the most effective way of reducing the vitreous pressure, that there is a direct relation between this reduction and age, and that there is no apparent correlation between the preoperative intraocular pressure and the vitreous pressure.
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PMID:Factors modifying vitreous pressure in cataract surgery. 730 72

The major intrinsic protein (MIP) of the vertebrate eye lens is the first identified member of a sequence-related family of cell-membrane proteins that appears to have evolved by gene duplication. Several members of the MIP family transport water (aquaporins), glycerol and other small molecules in microbial, plant and animal cells. Mutations in two aquaporin homologues of MIP underlie an autosomal recessive form of nephrogenic diabetes insipidus and absence of the Colton blood group antigens in humans, whereas, mutation of a third MIP-like gene underlies 'big brain' development in Drosophila. Here we show that distinct mutations in the murine Mip gene underlie one form of autosomal dominant cataract in the mouse. The cataract Fraser mutation is a transposon-induced splicing error that substitutes a long terminal repeat sequence for the carboxy-terminus of MIP. The lens opacity mutation is an amino-acid substitution that inhibits targeting of MIP to the cell-membrane. These allelic cataract mutations provide the first direct evidence that MIP plays a crucial role in the development of a transparent eye lens.
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PMID:Mutations in the founder of the MIP gene family underlie cataract development in the mouse. 856 64

Metabolic changes in the rabbit lens have been studied by means of nuclear magnetic resonance spectroscopy. These changes have been induced by prolonged topical treatment with dexamethasone. Our results demonstrate an increase in sorbitol, sorbitol-3-phosphate, fructose-3-phosphate, glycerol-3-phosphate and glucose-6-phosphate levels and a decrease in glutathione sulphate (GSH) and myo-inositol levels, in agreement with what was observed in lenses from streptozocin-diabetic rats before lens opacity. The hyperglycaemia can only partially explain all these observed biochemical variations. The lack of increase in the intermediates of pentose cycle, such as sedoheptulose-7-phosphate, seems to support the hypothesis of an inhibition of glucose-6-phosphate dehydrogenase by dexamethasone treatment. Finally dexamethasone treatment induces a decrease in GSH. The decreasing or the loss of GSH has been suggested as a possible pathogenic mechanism in the cataract formation.
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PMID:Metabolic changes in rabbit lens induced by treatment with dexamethasone. 1124 50

Lutein, a naturally occurring carotenoid, is widely distributed in fruits and vegetables and is particularly concentrated in the Tagetes erecta flower. Epidemiological studies suggest that a high lutein intake (6 mg/day) increases serum levels that are associated with a lower risk of cataract and age-related macular degeneration. Lutein can either be free or esterified (myristate, palmitate, or stearate). Both are practically insoluble in aqueous systems, and their solubility in food grade solvents (oils) is very limited, resulting is low bioavailability. To improve its solubility and bioavailability, lutein was solubilized in U-type food grade microemulsions based on ethoxylated sorbitan fatty acid esters, glycerol, R-(+)-limonene, and ethanol. Some of the main findings are as follows: (1) reverse micellar and W/O compositions solubilized both luteins better than an O/W microemulsion, and maximum solubilization is obtained within the bicontinuous phase; (2) free lutein is solubilized better than the esterified one, in the W/O microemulsions, whereas the esterified lutein is better accommodated within the O/W microemulsion; (3) vegetable oils decrease the solubilization of free lutein; (4) glycerol and alcohol enhance the solubilization of both luteins; (5) solubilization is surfactant-dependent in all mesophase structures, but its strongest effect is in the bicontinuous phase.
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PMID:Solubilization patterns of lutein and lutein esters in food grade nonionic microemulsions. 1470 12

Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a neurodegenerative disease marked by early-onset cataract and hearing loss, retinitis pigmentosa, and involvement of both the central and peripheral nervous systems, including demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC disease and we describe the clinical manifestations in a total of 19 patients from four different countries. The ABHD12 enzyme was recently shown to hydrolyze 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors CB1 and CB2. Our data therefore represent an example of an inherited disorder related to endocannabinoid metabolism. The endocannabinoid system is involved in a wide range of physiological processes including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation, and several potential drugs targeting these pathways are in development for clinical applications. Our findings show that ABHD12 performs essential functions in both the central and peripheral nervous systems and the eye. Any future drug-mediated interference with this enzyme should consider the potential risk of long-term adverse effects.
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PMID:Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of endocannabinoid metabolism. 2119 94


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