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 comparison of mammalian gamma-crystallins has been made by computer-graphics model building of several gamma-crystallin sequences based on the atomic co-ordinates of the X-ray determined structure of calf gamma-II crystallin. The complete family of rat gamma-crystallins is compared together with the orthologous protein, gamma 1-2 crystallin, from rat, human and calf lens, and the orthologous protein, gamma 2-1 crystallin, from rat and human lens. In human gamma-crystallins, a major structural difference, the replacement of an arginine by a cysteine, occurs in one of the four-fold repeated folded hairpins, which may affect stability. Sequence variations involving buried residues were observed, leading to small differences in core packing of the different sequences which may be related to their regional location in the lens. Model-building studies also indicate that the surfaces of the different gamma-crystallins vary in number of exposed hydrophobic residues and ion pairs. These differences would affect protein-water interactions and therefore contribute to refractive index. A major variable region of the gamma-crystallin structures involves polar residues surrounding the inter-domain contact and the length of the polypeptide connecting the two domains. An attempt is made to correlate bovine gamma-crystallins which are known to be responsible for cold cataract with the corresponding sequences from rat lens.
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PMID:Structural variation in mammalian gamma-crystallins based on computer graphics analyses of human, rat and calf sequences. 1. Core packing and surface properties. 373 18

Intumescent cataractous lenses were investigated as to their water content and protein composition. Nuclei were separated from cortices. Water-soluble, water-insoluble, urea-soluble and urea-insoluble portions were quantified and the subunit composition of the water-soluble crystallin fraction was looked at on SDS-gel electrophoresis. Compared to normal lenses it is observed that the water content in intumescent cataract is increased, water-soluble and urea-soluble fractions are diminished, whereas the urea-insoluble portions are augmented. No major changes are noted in the subunit composition of the soluble protein fractions. Particularly, the relative amount of gamma-crystallins is diminished in intumescent cataractous lenses.
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PMID:Lens proteins in intumescent cataract. 373 13

Physicochemical changes of the lens protein produced by UV light may be considered to be one of the pathogenic factors in the development of cataract. The effect of filters to eliminate these changes were investigated and evaluated using an in vitro system. UV irradiation caused degradation of alpha-crystallin to proteins with lower molecular weight, and thus the crystallin did not show insolubility. beta H- and beta L-crystallin showed insolubilization and aggregation with yellow coloration by photooxidation. The S-S linkage produced by oxidation of the SH group caused gamma-crystallin to aggregate and become insoluble. These chemical changes are prevented significantly by the UV-cutting colored filters.
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PMID:Effects of UV-cutting filters on aggregation of lens protein. 383 95

To determine the molecular mechanisms for cold cataract formation in the nucleus of the young mammalian lens, we have investigated the thermally reversible opacification of gamma-crystallin solutions isolated from calf lens. Coexistence curves (plots of opacification temperature Tc versus protein concentration) were determined for the individual gamma-crystallin fractions II, III, and IV as well as for the unfractionated gamma-crystallin mixtures isolated from the nucleus and cortex. The coexistence curve of gamma IV-crystallin is remarkably elevated above those of gamma II- and gamma III-crystallin and the gamma-crystallin mixtures. The gamma IV-crystallin fraction is the major determinant of the opacification temperature within the whole lens or isolated cytoplasm. Quasielastic light-scattering spectroscopy of gamma IV-crystallin solutions indicates that above Tc there are two populations of protein aggregates of distinctly different mean size. As the temperature is lowered towards Tc, both populations increase in size. Opacification occurs when the population of large scatterers, which is composed of less than 0.1% protein by weight, reaches an average radius of about 20,000 A.
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PMID:Opacification of gamma-crystallin solutions from calf lens in relation to cold cataract formation. 385 52

The reductone ascorbic acid, present in the crystalline lens in concentrations higher than those of glucose, is capable of undergoing nonenzymatic "browning" in the presence of lenticular proteins. We studied the nonenzymatic browning with ascorbate in model systems employing bovine serum albumin and lens crystallins. When bovine serum albumin, alpha-crystallin, or gamma-crystallin was incubated with [14C]ascorbic acid, the formation of yellow and then brown condensation products appeared to correlate with increasing protein-associated radioactivity. The fluorescence spectrum of these products was similar to that of homogenates of human cataractous lenses. We suggest that the nonenzymatic reaction of lens crystallins with ascorbic acid may contribute, at least in part, to the color changes of aging lenses and to the physical lenticular deterioration leading to senile cataract. High dietary intake of ascorbic acid did not affect the fluorescence spectrum of murine lenses; thus, we assume that the speed and extent of the lenticular browning reactions must depend on a deterioration of other factors of the multicomponent antioxidant system of the eye.
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PMID:The role of ascorbic acid in senile cataract. 386 54

Cataract disrupts the crystalline lens, a transparent, elastic, avascular, biconvex structure composed of a capsule, lens epithelium, and lens fiber cells. Many factors contribute to the progression of lens opacity, but aging is most frequently associated with cataract. As aging-related cataract develops, many biochemical and biophysical changes occur, most notably a marked increase in the insolubilization of the crystallin and extensive oxidation damage to many of the lens constituents. Cataract management should include ophthalmologic history and examination, medical evaluation, optical correction, control of ocular and systemic disease that may contribute to cataract, discontinuation of cataractogenic drugs, and periodic reexamination. Surgery is indicated when cataract is associated with vision decrease interfering with activities important to the patient, intraocular inflammation or glaucoma, or interference with management of posterior segment disease. More than 600 000 cataract operations are done in the United States each year; in 1982 an estimated 496 000 cataract operations were combined with intraocular lens implantation.
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PMID:Aging-related cataract: laboratory investigation and clinical management. 388 Oct 70

The Philly mouse develops a hereditary cataract about 5 weeks after birth. Although the causative agent is not known, data suggest that there is a correlation between cataract formation and the selective absence of a 27 kilodalton (27K) beta-crystallin lens polypeptide. The ontogeny of the 27K beta-crystallin polypeptide was examined in normal mice in order to evaluate its role in normal development and determine what impact its absence may have on the Philly mouse lens. A monoclonal antibody was used with the PAP method to immunocytochemically localize the 27K polypeptide in lenses of normal mice during development. beta-Crystallins detected with polyclonal antisera were found in differentiated fiber cells throughout the lens. In contrast, the 27K beta-crystallin polypeptide detected with a specific monoclonal antibody was not found in the fiber cells of the inner part of the lens (nucleus), but was specifically localized in the fiber cells of the outer part of the lens called the cortex. The polypeptide was found only in elongating and differentiated fiber cells and not in mitotically active epithelial cells. Although a minor component of the 2-day-old lens, the 27K polypeptide comprised a large portion of the 16-day-old lens including the anterior and posterior poles. These data show that the 27K polypeptide is a minor component of the embryonic lens, but becomes a major contributor to the postnatal lens. The 27K beta-crystallin lens polypeptide is abundant in the fiber cells of the normal postnatal mouse lens. The absence of the 27K polypeptide in the Philly mouse may contribute to the observed failure of fiber cells to differentiate in the Philly mouse after birth or may be deleterious in some other manner to normal lens development. The selective absence of the 27K beta-crystallin polypeptide, a defect which precedes cataract formation in the Philly mouse, is intriguing since it suggests a relationship between this major lens polypeptide and lens clarity.
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PMID:Immunocytochemical localization of the 27K beta-crystallin polypeptide in the mouse lens during development using a specific monoclonal antibody: implications for cataract formation in the Philly mouse. 394 59

The eye lens of the Fraser mouse contains a dominantly inherited cataract with reduced amounts of seven distinct but homologous gamma crystallins encoded by a family of gamma-crystallin genes. The results of experiments with cultured lenses, cell-free RNA translation, and Northern blot hybridization indicated a specific loss of the family of gamma-crystallin messenger RNA's in the Fraser mouse lens. Southern blot hybridization of genomic DNA's from normal and Fraser mice showed no differences in gamma-crystallin coding sequences.
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PMID:Selective loss of a family of gene transcripts in a hereditary murine cataract. 396 60

Water-soluble and water-insoluble polypeptides from nuclei of clear vs. opaque and brunescent human lenses were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretically transferred to nitrocellulose paper. Treatment of the nitrocellulose blots with monospecific antisera to human alpha and beta crystallin and to antisera against the Major Intrinsic Polypeptide (MIP26) of lens membrane demonstrated no difference in binding between microdissected sections of clear vs. opaque (and brunescent) nuclei. In contrast, treatment of nitrocellulose blots with monospecific antisera to human gamma crystallin demonstrated little or no binding to polypeptides from opaque (and brunescent) nuclei as compared with age-matched clear nuclei. These results demonstrate the selective involvement of gamma crystallins in opacification (and brunescence) in the human lens nucleus, and strongly suggest the presence of covalent changes of the gamma crystallin molecule during development of the human nuclear cataract.
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PMID:Characterization of polypeptides from human nuclear cataracts by Western blot analysis. 397 61

Incubation of lens in Ca2+-containing media, considered by several investigators to be a useful model of cataract formation, gave rise to significant alterations in the covalent structures of various proteins. In rabbit lens, when sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used after reduction of disulfides in urea, the most readily observable changes were (i) disappearance of 210K, 95K, and 60K proteins, (ii) modifications of alpha crystallin subunits, (iii) alterations of beta H crystallins, and (iv) de novo production of 55K and higher molecular weight polymers. The addition of leupeptin inhibited the disappearances of 210K, 95K, and 60K proteins and the alteration of alpha crystallins, suggesting that all these were caused by a Ca2+-activated protease. The proteolytically sensitive 60K species was identified as vimentin, a component of intermediate filaments. Formation of the 55K material and of higher molecular weight polymers during Ca2+ treatment of the lens could be prevented by histamine, a compound known to inhibit the transglutaminase-mediated cross-linking of proteins by epsilon-(gamma-glutamyl)lysine peptide bonds in other biological systems. It could also be shown by immunoblotting that an antibody raised against the 55K material reacted selectively with beta crystallins of normal lens. This indicates that the 55K product is in all likelihood an essential intermediate toward higher polymers and that the 55K product is a cross-linked dimer of certain polypeptides of beta crystallin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Formation of a 55 000-weight cross-linked beta crystallin dimer in the Ca2+-treated lens. A model for cataract. 398 92


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