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Query: UMLS:C0086543 (cataract)
29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cataractous and noncataractous human lenses were irradiated with ultraviolet (UV) light, and the resulting triplet and radical species were studied by electron paramagnetic resonance spectroscopy. Evidence is presented that free radicals are produced by a biphotonic process involving tryptophan as an intermediate triplet. This makes free radical production energetically feasible. A possible link between incident UV light and cataract formation is suggested.
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PMID:Free radicals produced in human lenses by a biphotonic process. 21 85

I have discussed five aspects of lens metabolism and their possible relationship to cataract in man, and this has left me with five fundamental questions to be answered. 1. Are the fluorescent tryptophan derivatives, found only in the lens of man and higher primates, involved in the development of brown nuclear cataract? 2. Is naphthalene cataract in rabbits a model for any type of cataract in man--i.e., are quinones ever formed in the human eye? 3. Is diabetes the only cataract in which osmotic swelling is important? 4. Does self-digestion of protein in the human lens contribute to cataract development? 5. Are the consequences of the abnormal maturation of lens fibers, which occurs in tryptophan deficiency cataract in rats, ever seen in man?
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PMID:Experimental studies on cataract. 96 16

Cultured rabbit lenses were irradiated with UV (311 nm peak; 295-340 nm) for 30 to 60 min. The entire spectrum lies in the near-UV, the major component is UVB, with a minor portion (25%) of UVA, and is henceforth referred to as near-UV(B). Posterior irradiation caused no cataract and no significant ionic imbalances compared to anterior irradiation, which caused opacification and marked changes in sodium and calcium concentrations. Anterior irradiation also resulted in reduced Na/K-ATPase activity in the epithelium. ATPase activity was not immediately inhibited; rather, only after culture was enzyme activity reduced. The concentration of reduced glutathione (GSH) decreased rapidly in the epithelium and more slowly in the underlying lens fibers. Loss of GSH was more rapid and extensive when irradiation occurred in the presence of oxygen. Irradiation under anaerobic conditions resulted in opacification but was considerably less extensive than when irradiation of lenses occurred in the presence of 7% oxygen. Near-UV(B) damage following anaerobic irradiation and 20 hrs of culture resulted in an increase in sodium levels and loss of GSH; calcium levels were not significantly elevated. Since irradiation of tryptophan solutions produced small amounts of hydrogen peroxide, the possibility of hydrogen peroxide-mediated damage was investigated but no role could be substantiated. Peroxide detoxification by the epithelium of near-UV(B) cataracts was observed, as measured by its ability to eliminate hydrogen peroxide added as a bolus.
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PMID:Mechanisms involved in cataract development following near-ultraviolet radiation of cultured lenses. 132 94

Short-term incubation of bovine alpha-crystallin with ascorbate alters the protein conformational stability. The denaturation curves with urea and guanidinium-chloride show different patterns, suggesting a deviation from a two-state mechanism owing to the presence of one or more intermediates in the unfolding of ascorbate-modified alpha-crystallin. Furthermore, the latter protein profiles are shifted to lower denaturant concentrations indicating a destabilizing action of ascorbate, which is capable of facilitating protein dissociation into subunits as demonstrated by gel filtration with 1.5 M-urea. The decrease in conformational stability cannot be ascribed to any major structural alteration, but rather to localized changes in the protein molecule. In fact, no difference between native and ascorbate-treated alpha-crystallin can be detected by amino acid analysis but perturbation of the tryptophan and tyrosine environment is indicated by alterations in intrinsic fluorescence. Furthermore, turbidity and light-scattering measurements suggest an involvement of the lysine side chains, since aggregability patterns with acetylsalicylic acid are significantly altered. The ascorbate-destabilizing effect on the conformational stability of alpha-crystallin, probably exerted through oxidative modification of amino acid residues and/or the formation of covalent adducts, provokes unfavourable steric interactions between residues along the polypeptide chains, thus favouring aggregation and insolubilization of crystallins which can lead to cataract formation, as also demonstrated by proteolytic digestion patterns which show a lower rate of degradation of the ascorbate-modified alpha-crystallin.
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PMID:Conformational stability of bovine alpha-crystallin. Evidence for a destabilizing effect of ascorbate. 141 62

Water-soluble crystallins were obtained from clear human lenses of different age (4-81-year-olds) and lenses of individuals showing senile or diabetic cataracts. Levels of early glycation products were high in the high molecular weight material (HM) and the alpha-crystallin fractions, compared with beta- and gamma-crystallins. This difference becomes more prominent upon aging. The content of total early glycation products in HM and alpha-crystallin increases clearly with age, whereas levels remain relatively constant in the beta- and gamma-crystallins. There is an elevation of early products in cataractous lenses from diabetic individuals compared with those suffering from senile cataract. Specific non-tryptophan fluorescence (excitation/emission wavelengths 370/440 nm), used as an indicator for late glycation products, increased dramatically with age and was 2-fold higher in the diabetic subjects. Levels of fluorescence decreased in the order HM > alpha- > beta- > gamma-crystallins. The results suggest an increase in glycation rate in alpha-crystallin as a result of aging and diabetes, while the rate of glycation of beta- and gamma-crystallins remains almost constant.
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PMID:Glycation of crystallins in lenses from aging and diabetic individuals. 145 95

Since most of the known factors that are associated with cataract formation are oxidative in nature, one would expect that a highly reductive environment might arrest or retard the progress of cataract formation. Reduced nucleotides, both NADH and NADPH, are potent reductants with a large negative redox potential of -320 mV. Lenses of certain species contain high levels of these nucleotides, presumably due to the presence of taxon specific crystallins. We have utilized this situation to investigate whether the levels of reduced pyridine nucleotides modulate photo-oxidative damage to the lens. We have monitored the time dependent loss of tryptophan fluorescence upon photodamage for lenses from guinea pig, rabbit and frog (Rana) that contain high levels of pyridine nucleotides and compared with the lenses from rat, Xenopus and a mutant strain of guinea pig that contain significantly lower amounts of these nucleotides. About 75% and 90% of the initial fluorescence intensity is lost in the case of rat and Xenopus lenses, respectively, after a total of 35 min exposure. Rabbit, guinea pig and frog lenses, under identical conditions, show only about 35-40% loss of the initial fluorescence. It appears that the lenses that contain high levels of reduced nucleotides are less susceptible to photodamage. The observed anti-oxidative role of reduced nucleotides in the lenses indicates the possibility of testing reductants (NADPH, NADH and their functional analogues) as potential candidates to therapeutically intervene in the process of cataractogenesis.
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PMID:Levels of reduced pyridine nucleotides and lens photodamage. 145 82

Fluorometric studies of cataractous and non-cataractous human lenses were carried out to study the emission characteristics and the distribution and solubility of lenticular pigments. Most of the detected fluorophores were well distributed over the cortical and nuclear portion of the lens. The decrease in solubility of proteins with aging and cataract formation is concomitant with increasing photolysis of tryptophan. However, this is likely a phenomenon independent of the photochemical transformations of the lens proteins. The number of emitting species in the diseased lenses are higher than in the normal mature lenses. A species emitting around 375 or 388 nm is of particular interest (lambda cx 330 nm) in that the emission characteristics of this fluorophore resemble kynurenic acid which has a high photosensitizing efficiency. The concentration of fluorescent pigments in the lenses of Indian origin is significantly high. The intense pigmentation could be attributed largely to the formation of photoproducts in the absence of normal endogenous antioxidant accumulation that is dependent on nutrition standard. If, indeed, any of these fluorescent pigments, because of their photosensitizing ability, are responsible for lenticular opacity, it is not the abundance of sunlight alone but also malnutrition that could account for the high incidence of cataract in India.
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PMID:Studies on human lenses: II. Distribution and solubility of fluorescent pigments in cataractous and non-cataractous lenses of Indian origin. 152 89

One of the research programs of the Australian Cataract Research Foundation (ACRF) is aimed at investigating the possibility that senile cataract both cortical and nuclear, may result from the interaction of reactive metabolites with proteins in the lens. In particular we are exploring the potential role of tryptophan metabolites for example, 3-hydroxyanthranilic acid, in this disease. This article examines briefly some aspects of this approach.
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PMID:Reactive metabolite hypothesis for human senile cataract. 191 40

Age-related cataract is a condition characterized by multiple mechanisms and multiple risk factors. The mechanisms that bring about a loss in transparency include oxidation, osmotic stress, and chemical adduct formation. Risk factors for cataract include diabetes, radiation (ultraviolet B, x-ray), certain pharmaceutical substances, certain nutritional states, and possibly acute episodes of dehydration. Interaction occurs between and among mechanistic factors and risk factors. Thus nutrition must be considered as one part of a tapestry of intertwined events and responses. Certain experimental models for nutritional cataract have been useful for study of the cataractogenic process but are probably not important factors in the human disease. Little current evidence supports significant roles in human senile cataract for imbalances of tryptophan or other amino acids, deficiencies of calcium or selenium, or excessive intake of selenium. Overconsumption of galactose is likely to be hazardous only in subjects with genetic inability to metabolize this sugar. Vitamins with antioxidant potential (riboflavin, vitamin E, vitamin C, carotenoids) deserve further research scrutiny to ascertain their significance in cataract etiology. Excessive caloric intake needs to receive added emphasis as a factor contributing to cataract. Diabetes increases the likelihood of cataract three- to four-fold. Obesity, defined as more than 20% overweight, is considered a major risk factor for non-insulin-dependent, or type II, diabetes (69, 73). Weight control can be recommended as a prudent, safe, economic, and effective means of lowering risk probability for diabetes and the associated complication of cataract.
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PMID:Nutritional factors in cataract. 220 Apr 64

After the lens is removed in cataract surgery, the vitreous presumably receives all of the ambient 300-nm light that has filtered through the cornea. Using this model for aphakic eyes, we progressively irradiated intact vitreous samples of a 49-year-old human with 300-nm light and monitored changes in absorption, fluorescence, and circular dichroism (CD) properties. CD and fluorescence measurements of unirradiated vitreous samples showed a) a strong tryptophan fluorescence band of non-collagenous protein at 336 nm and a very weak band around 430 nm due to N-formylkynurenine (N-FK), a photoproduct of tryptophan, and b) a strong, negative CD band below 250 nm representing a composite spectrum of hyaluronic acid, collagen, and non-collagenous protein. Upon irradiation, the tryptophan emission band at 336 nm progressively decreased with time and the band maximum was concomitantly red-shifted; the N-FK fluorescence band at 430 nm, on the other hand, continually increased with the time of irradiation. A significant increase in the fluidity (liquefaction) of the vitreous gel also was noted upon irradiation, a change that was monitored successfully by measuring the progressive decrease in the polarization value of tryptophan fluorescence. The extent of liquefaction, measured spectroscopically, was found to be 40% upon irradiation for 10 hr. In addition, CD measurements indicated a partial loss in the secondary structure of the non-collagenous protein.
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PMID:Liquefaction of human vitreous in model aphakic eyes by 300-nm UV photolysis: monitoring liquefaction by fluorescence. 238 1


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