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)

Human cataract lens crystallins are crosslinked and demonstrate a non-tryptophan blue fluorescence. We report here that exposure of lens crystallin to H2O2 within the concentration range reported for human aqueous humor, produces crosslinking of crystallin polypeptides within 10 minutes in the presence of the heme-undecapeptide from cytochrome c. Concomitantly, a blue fluorescence develops. These findings suggest the possibility that under some conditions hydrogen peroxide activation may play a role in cataractogenesis in vivo.
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PMID:The rapid H2O2-mediated nonphotodynamic crosslinking of lens crystallins generated by the heme-undecapeptide from cytochrome C: potential implications for cataractogenesis in man. 630 94

The mechanism of oxidative damage to the lens through intraocular photochemical generation of superoxide and its derivatization to other oxidants such as singlet oxygen, hydroxyl radical and hydrogen peroxide has been studied. Rat lenses when organ cultured aerobically in TC 199 containing additional amounts of riboflavin were damaged as demonstrated by an inhibition of the uptake of Rb 86 against a concentration gradient. The pump was not affected by light if the culture was conducted in the basal TC 199. However, light was observed to induce significant peroxidative degradation of the tissue lipids even in the basal medium, the degradation being indicated by the formation of malonaldehyde. Both the inhibition of the pump as well as the peroxidative degradation of the tissue lipids, were attenuated considerably by scavengers of superoxide and hydrogen peroxide. In addition, the lipid degradation was prevented by vitamins C and E. The results suggest that the photodynamic injury to the lens cation pump as well as to membrane lipids is incumbent upon an initial generation of superoxide and its derivatization to other oxidants. Thus, the ocular lens is susceptible to oxidative insult and physiological damage through photocatalytic generation of various oxygen radicals. Large concentrations of ascorbic acid in the aqueous humor seems to be able to provide significant protection against such an insult. Thus, this may be one of the functions of high concentration of ascorbic acid in the aqueous humor. The implication of oxidative stress has also been examined in the genesis of cataracts in vivo. Treatment with vitamin E of the Emory mouse led to a decrease in the rate of cataract progression suggesting that at least in some instances an oxidative stress could participate in the formation of cataracts. Oxygen radicals may inflict damage at multifarious biochemical sites. Human lens lipids were also shown to have an absorption maxima at 239 nm indicating their susceptibility to oxidative degradation. In addition the lipid extract has fluorescence similar to that of lipofuscins. The levels of MDA were higher in the brunescent cataracts as compared to that in the nonbrunescent cataracts. The implications of oxidative stress towards the genesis of cataracts in humans is being explored further.
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PMID:Oxidative stress on lens and cataract formation: role of light and oxygen. 636 May 40

Reversible "cold cataract" phenomenon of a SD-strain rat lens (29 days old) was studied by Raman spectroscopy in the temperature range of 35-17.5 degrees C. Cold cataract appeared in the lens nucleus below 26 degrees C. The Raman spectra did not show any detectable change in the 300-800 cm-1 and 900-4000 cm-1 regions as the temperature decreased. However lens opacification caused a significant change in the intensity ratio of tyrosine doublet near 840 cm-1, suggesting that some tyrosine residues in lens proteins undergo a change in their hydrogen bonding environment during the cold cataract formation. It was also found that the intensity ratio of the tyrosine doublet band provides a practical indicator of phase transition temperature of cold cataract.
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PMID:Raman spectroscopic evidence for the microenvironmental change of some tyrosine residues of lens proteins in cold cataract. 671 81

Previous studies have shown that cell uncoupling is paralleled by an increase in tightness and crystallinity of gap junction particle arrays. Gap junction crystallinity is believed to be part of the uncoupling mechanism because it can be produced in gap junctions isolated from lens fibers on direct exposure to uncoupling agents such as divalent cations or hydrogen ions. Some doubts, however, have been raised on the capacity of lens fiber junctions to crystallize and uncouple in situ. The present study shows that the gap junctions of rat lens fibers indeed crystallize after a treatment that increases drastically the membrane permeability to ions. The treatment consists of a brief immersion of the lenses in liquid nitrogen, followed by incubation for several hours in Tyrode's solution at 37 degrees C. Immediately after liquid nitrogen treatment, the lenses start gaining sodium and calcium while losing potassium, and eventually become opaque. Addition of 10 mM EDTA to calcium and magnesium-free Tyrode's solutions inhibits particle crystallization and lens cataract, whereas low concentrations of EDTA (1 mM) are not effective. These findings, together with preliminary data on the capacity of lens fibers to heal over, indicate that the gap junctions of lens fibers are capable of crystallizing and uncoupling in situ.
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PMID:Gap junction crystallization in lens fibers after an increase in cell calcium. 678 27

Raman spectra have been measured for the lenses from cac-strain mice. These mice possess a hereditary defect and provide lenses at various stages of opacification. The Raman spectra of normal mouse lenses have been obtained also for comparison purposes. The amide I and III bands appear in very similar positions in the Raman spectra of cataractous and normal lenses, suggesting that the peptide backbone of main lens proteins does not undergo a major conformational change upon lens opacification. However, lens opacification causes significant changes in the intensity ratio of the tyrosine doublet near 840 cm-1 and in that of the Raman bands at 881 and 760 cm-1 due to tryptophan residues. These changes could be observed even in the incipient stage of hereditary cataract and became more pronounced with cataract development. These observations indicate that in the course of lens opacification some tyrosine residues undergo a change in their hydrogen-bonding environment and some buried tryptophan residues became exposed. In addition, the present Raman spectroscopic study provides insight into the 2SH leads to S-S conversion in lens proteins. It was found that the conversion proceeded at a faster rate in a hereditary cataractous lens than in a normal lens; however, this difference was fairly small at the early stage of cataract development. Importantly, the 2SH leads to S-S conversion was accelerated after nuclear cataract formation. These observations support the hypothesis that the formation of S-S linkages is not a predominant factor for initiating lens opacification. Probably the formation of S-S linkages plays an important role in stabilizing the protein aggregates which are the cause of lens opacification. The intensity of the SH stretching mode (2579 cm-1) was very weak or absent in the Raman spectrum of a well-developed cataractous lens, suggesting that most sulfhydryl groups form disulfide bonds. Moreover, the fact that this occurs without major conformational changes of peptide backbones implies that most cysteine residues in lens crystallins are accessible to solvent or are clustered closely together.
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PMID:Structural changes in the lens proteins of hereditary cataracts monitored by Raman spectroscopy. 684 84

Caffeic acid phenethyl ester (CAPE) was isolated from propolis (a product of honeybee hives) that has been used in folk medicine as a potent antiinflammatory agent. CAPE is cytotoxic to tumor and virally transformed but not to normal cells. Our main goal was to establish whether CAPE inhibits the tumor promoter (12-O-tetradecanoylphorbol-13-acetate)-induced processes associated with carcinogenesis. Topical treatment of SENCAR mice with very low doses (0.1-6.5 nmol/topical treatment) of CAPE strongly inhibits the following 12-O-tetradecanoylphorbol-13-acetate-mediated oxidative processes that are considered essential for tumor promotion: (a) polymorphonuclear leukocyte infiltration into mouse skin and ears, as quantified by myeloperoxidase activity; (b) hydrogen peroxide (H2O2) production; and (c) formation of oxidized bases in epidermal DNA, as measured by 5-hydroxymethyluracil and 8-hydroxylguanine. A 0.5-nmol dose of CAPE suppresses the oxidative burst of human polymorphonuclear leukocytes by 50%. At higher doses (1-10 mumol), CAPE inhibits edema and ornithine decarboxylase induction in CD-1 and SENCAR mice. Interestingly, we discovered that 12-O-tetradecanoylphorbol-13-acetate-induced H2O2 production in bovine lenses also is inhibited by CAPE. Cumulatively, these findings point to CAPE as being a potent chemopreventive agent, which may be useful in combating diseases with strong inflammatory and/or oxidative stress components, i.e., various types of cancer and possibly cataract development.
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PMID:Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester. 768 Feb 81

Cataract is a major ocular disease that causes blindness in many developing countries of the world. It is well established that various factors such as oxidative stress, UV, and other toxic agents can induce both in vivo and in vitro cataract formation. However, a common cellular basis for this induction has not been previously recognized. The present study of lens epithelial cell viability suggests such a general mechanism. When lens epithelial cells from a group of 20 cataract patients 12 to 94 years old were analyzed by terminal deoxynucleotidyl transferase (TdT) labeling and DNA fragmentation assays, it was found that all of these patients had apoptotic epithelial cells ranging from 4.4 to 41.8%. By contrast, in eight normal human lenses of comparable age, very few apoptotic epithelial cells were observed. We suggest that cataract patients may have deficient defense systems against factors such as oxidative stress and UV at the onset of the disease. Such stress can trigger lens epithelial cell apoptosis that then may initiate cataract development. To test this hypothesis, it is also demonstrated here that hydrogen peroxide at concentrations previously found in some cataract patients induces both lens epithelial cell apoptosis and cortical opacity. Moreover, the temporal and spatial distribution of induced apoptotic lens epithelial cells precedes development of lens opacification. These results suggest that lens epithelial cell apoptosis may be a common cellular basis for initiation of noncongenital cataract formation.
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PMID:Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals. 779 Mar 71

Hydrogen peroxide, in concentrations of 10-1000 microM, produces two major changes in the current-voltage relationships associated with the equatorial potassium current of the lens. First, the resting and reversal potentials become more negative than they were prior to treatment with hydrogen peroxide and second, the membrane resistance related to the equatorial current is decreased. The shift in the resting and reversal potentials is in the opposite direction from that produced by ouabain. Based on the Nernst equation, the shift in the reversal potential suggests that there is an increase in the concentration of potassium in the lens. The 86Rb uptake and efflux are increased. These observations suggest that hydrogen peroxide stimulates the Na,K-pump. The decrease in membrane resistance is inhibited by 100 microM of quinine, a calcium-dependent potassium channel blocker, and does not decrease in a calcium-free medium. This suggests that the decrease in resistance may be secondary to an increase in lenticular calcium. These effects of hydrogen peroxide are similar to those of p-chloromercuriphenylsulfonate (pCMPS), a nearly impermeant sulfhydryl binding agent, and suggest that permeant hydrogen peroxide may increase calcium influx by acting on sulfhydryl groups on the outer surface of lens membranes. Verapamil, a calcium channel blocker, is reported to prevent cataract formation. D600, the methoxy analogue of verapamil, is a calcium channel blocker that increases the resistance associated with the equatorial current in the presence and absence of hydrogen peroxide. The gadolinium ion has a similar effect. Thus, D600 and Gd3+ partially counteract the reduction in membrane resistance produced by 50 microM hydrogen peroxide.
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PMID:Effects of hydrogen peroxide oxidation and calcium channel blockers on the equatorial potassium current of the frog lens. 817 48

Proton nuclear magnetic resonance (1H-NMR) is one of the most important methods for noninvasively evaluating the state of water in the biological system. It could be useful for evaluation of the early changes of cataract. In this study, in vivo magnetic resonance imaging (MRI) was applied to rat galactosemic cataract, which is a model of the human diabetic cataract, and compared with the histological findings. The relationship between the relaxation times (T1, T2) and the water contents were discussed. The T1 and T2 values were prolonged and the high intensity area of the lens cortex was enlarged from the early stage of the cataract (two days after the intake of galactose). These changes preceded the histological changes. This suggests that MRI is applicable for the evaluation of anti-cataract agents, for example aldose reductase inhibitors, against human diabetic cataract.
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PMID:[Magnetic resonance imaging study on rat sugar cataract]. 825 67

The purpose of these experiments was to examine the relationship between oxidation cataract and proteolysis in cultured rat lens. Hydrogen peroxide cataract showed insolubilization of protein, loss of 31 kDa beta B1-crystallin polypeptide, decreases in soluble calpain, and increases in insoluble calpain. This suggested that calpain may be activated in hydrogen peroxide treated lenses, since beta B1 is a known calpain substrate, and calpain undergoes autolysis and degradation when activated. Furthermore, the cysteine protease inhibitor E64 was partially effective in preventing development of H2O2-cataract. E64 also prevented the loss of the 31 kDa beta B1-crystallin polypeptide and decreased the loss of calpain in the lens. These results suggested that development of hydrogen peroxide induced cataract in rat lenses was associated with activation of calpain.
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PMID:Role of calpain in hydrogen peroxide induced cataract. 831 93


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