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)

A new hereditary defect of tryptophan metabolism is described in a Sudanese family with a high degree of consanguinity. It has an autosomal recessive pattern of inheritance. The condition manifests as a pellagra-like skin rash within 8 weeks after birth, with signs of cerebellar ataxia and developmental retardation. Cataracts develop early, and to date none of the ten affected children has survived beyond 2 years of age. Biochemically, the condition is characterized by an apparent impairment of the ability to synthesize quinolinic acid and nicotinamide nucleotides from tryptophan, which might be due to abnormally high activity of the enzyme picolinate carboxylase.
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PMID:Lethal familial pellagra-like skin lesion associated with neurologic and developmental impairment and the development of cataracts. 405 88

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

The excised rat crystalline lens opacified when incubated aerobically with phenazine methosulfate, but no opacification was observed under anaerobic conditions. Morphological studies revealed development of opacification in the cortex. The opacification resembled that often seen in the early period of senile cataract as well as in naphthalene-induced and UV cataract. Both an increase in hydration and in electrolyte imbalance accompanied this opacification. Na,K-ATPase activity of the opacified lens was found to decrease. In order to investigate if activated oxygen is involved in these processes, we conducted an electron spin resonance study by means of a spin trapping technique. When the lens homogate was incubated with phenazine methosulfate, OH radicals were generated under aerobic but not under anaerobic conditions. Reduced pyridine nucleotides must be involved in the process, because the mixture of nicotinamide adenine dinucleotide phosphate [NAD(P)] and phenazine methosulfate did not generate OH radicals, but the mixture of NAD(P)H and phenazine methosulfate generates OH radicals, indicating that reduced phenazine methosulfate was involved in the OH radical generation. Probably, the generated OH radicals inactivated Na,K-ATPase residing in the epithelium of the lens, which eventually caused opacification of the lens. The present experiment system may be used for the elucidation of lens opacification (cataract) involved with reactive oxygen species.
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PMID:Reactive oxygen species involved in phenazine-methosulfate-induced rat lens opacification. An experimental model of cataract. 813 88

Aldose reductase (AR) has been implicated in the etiology of the secondary complications of diabetes. This enzyme catalyzes the reduction of glucose to sorbitol using nicotinamide adenine dinucleotide phosphate as an essential cofactor. AR has been localized at the sites of tissue damage, and inhibitors of this enzyme prevent the development of neuropathy, nephropathy, retinopathy, and cataract formation in animal models of diabetes. The crystal structure of AR complexed with zopolrestat, a potent inhibitor of AR, has been described.(1) We have generated a model of the AR-inhibitor complex based on the reported Calpha coordinates of the protein and results of a structure-activity relationship study using four structurally distinct classes of inhibitors, recombinant human AR, and four single-site-directed mutants of this enzyme. The effects of the site-directed mutations on residues within the active site of the enzyme were evaluated by average interaction energy calculations and by calculations of carbon atom surface area changes. These values correlated well with the IC(50) values for zopolrestat with the wild-type and mutant enzymes, validating the model. On the basis of the zopolrestat-binding model, we have proposed binding models for 10 other AR inhibitors. Our models have enabled us to gain a qualitative understanding of the binding domains of the enzyme and how different inhibitors impact the size and shape of the binding site.
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PMID:Molecular modeling of the aldose reductase-inhibitor complex based on the X-ray crystal structure and studies with single-site-directed mutants. 1073 39

Tobacco consumption is the leading preventable cause of disease, disability, and premature death but little is known about its deleterious effect on the ocular health of workers handling tobacco. The goal of this study was to identify probable effects of occupational tobacco exposure among south Indian bidi-industry workers. This study included 310 females (mean age, 34.8 +/- 10.9 years) actively involved in bidi-rolling presenting with eye symptoms to a tertiary eye care hospital. Results suggested that a wide spectrum of ocular complications exist among these workers. Common ocular symptoms were defective vision, dull-aching headache and eye irritation. The main ocular findings were papillary conjunctival hyperplasia, hyperpigmentation of ocular surface, punctate epithelial erosion or superficial punctate keratitis, cataract or pseudophakia and segmental optic atrophy. Abstaining from work, supplementation of Vitamin B complex rich in B 12 and appropriate surgical or medical management reversed visual loss due to corneal disease or cataract but was not effective in optic neuropathy.
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PMID:Ocular manifestations in bidi industry workers: possible consequences of occupational exposure to tobacco dust. 1857 93

Elevated plasma Homocysteine level is an independent risk factor for age related (senile) cataract. Certain nutritional deficiencies, in particular Folate, Vitamin B(12), Vitamin B(6) relate inversely with Homocysteine level. This study was undertaken to evaluate the plasma level of Vitamin B(12), Folate, and Homocysteine of cataract patients and to study the interplay between them. Serum Homocysteine level is significantly increased in cataract patients when compared with control (p< 0.001). There was a significant decrease in the level of Folate as compared with control (p<0.001). There was a negative correlation between Homocysteine vs. Vitamin B(12) (p<0.01) and Folate (p<0.01) in the Cataract patients. Our findings suggest that increased plasma Homocysteine level is associated with decreased plasma levels of Folate and VitaminB(12) in Cataract patients, which might have a possible role in the root cause of cataract pathogenesis.
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PMID:Plasma Homocysteine, Folate and Vitamin B(12) levels in senile cataract. 2310 65

The sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases that helps regulate the lifespan of diverse organisms. The human genome encodes seven different sirtuins (SIRT1-7), which share a common catalytic core domain but possess distinct N- and C-terminal extensions. Dysfunction of some sirtuins have been associated with age-related diseases, such as cancer, type II diabetes, obesity-associated metabolic diseases, neurodegeneration, and cardiac aging, as well as the response to environmental stress. SIRT1 is one of the targets of resveratrol, a polyphenolic SIRT1 activator that has been shown to increase the lifespan and to protect various organs against aging. A number of animal studies have been conducted to examine the role of sirtuins in ocular aging. Here we review current knowledge about SIRT1 and ocular aging. The available data indicate that SIRT1 is localized in the nucleus and cytoplasm of cells forming all normal ocular structures, including the cornea, lens, iris, ciliary body, and retina. Upregulation of SIRT1 has been shown to have an important protective effect against various ocular diseases, such as cataract, retinal degeneration, optic neuritis, and uveitis, in animal models. These results suggest that SIRT1 may provide protection against diseases related to oxidative stress-induced ocular damage, including cataract, age-related macular degeneration, and optic nerve degeneration in glaucoma patients.
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PMID:The role of SIRT1 in ocular aging. 2389 78