The Lens: Development, Proteins, Metabolism and Cataract

Harding, John J.; Crabbe, M. James C.

doi:10.1016/b978-0-12-206921-5.50008-8

Cited by 221 publications

(173 citation statements)

References 1,511 publications

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“…In the present survey, we have sought to identify those gene expression differences between clear human lenses relative to age-related cataracts and we have focused on the lens epithelium since this monolayer of cells is essential for the growth, differentiation and homeostasis of the entire organ (Bloemendal, 1981;Piatigorsky, 1981), contains the highest levels of enzymes and transport systems in the lens (Reddy, 1971;Reddan, 1982;Spector, 1982) and is the first part of the lens exposed to environmental insults (Reddan, 1982;Spector, 1982). Multiple studies suggest that the lens epithelium is capable of communicating with the underlying fiber cells (Rae et al, 1996) and direct damage to the lens epithelium and its enzyme systems is known to result in cataract formation (Harding and Crabbe, 1984;Hightower, 1995;Spector, 1995;Phelps Brown, 1996). Importantly, the majority of transcription occurs in the epithelial cells of the lens, and therefore these cells make up the majority of lens cells capable of responding to environmental insults and/or the presence of cataract through altered gene expression.…”

Section: Introductionmentioning

confidence: 99%

Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses and aged human lenses

Hawse

Hejtmancik

Horwitz

et al. 2004

Experimental Eye Research

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We have examined the gene expression profiles of young, old and cataractous human lenses in order to differentiate those gene expression changes specific for cataract from those also associated with lens aging. Differentially expressed transcripts were identified by oligonucleotide microarray analysis and clustered according to their known functions. Four hundred and twelve transcripts that are increased and 919 transcripts that are decreased were identified at the 2-fold or greater level between epithelia isolated from cataract relative to clear lenses while 182 transcripts that are increased and 547 transcripts that are decreased were identified at the 2-fold or greater level between young and old lens epithelia. Comparison of the cataract gene expression changes with those detected in lens aging revealed that only 3 transcripts exhibited similar trends in gene expression. These data suggest that cataract-and age-specific changes in gene expression do not overlap and provide evidence for multiple cataract-and age-specific gene expression changes in the human lens.

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Section: Introductionmentioning

confidence: 99%

Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses and aged human lenses

Hawse

Hejtmancik

Horwitz

et al. 2004

Experimental Eye Research

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“…Introduction phate-utilising enzymes and addition of labeled G-6-P to a crude lens lysate would therefore yield a large number of different labeled prodXylose-fed young rats accumulate polyols, including xylitol ucts, making it difficult to identify any inositol-l-phosphate produced, myo-Inositol-phosphate synthetase has been reported in [1] and develop cataractous lesions. Kinoshita and colleagues non-lens tissues as having a molecular mass of approx.…”

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confidence: 99%

Accumulation of xylitol in the mammalian lens is related to glucuronate metabolism

1996

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Cataract remains the major cause of blindness worldwide and a common complication of diabetes. Polyol Preparation of lens lysates accumulation in the lens is associated with cataract formation.Freshly dissected bovine or rat lenses were homgenised in 2 ml of a Here we present evidence for a novel pathway for xylitol suitable ice-chilled assay buffer, using a manual Braun Homogeniser. production in the lens involving glucuronate metabolism. Xylitol Membranes and cell debris were removed by brief centrifugation in a can be produced in rat and bovine lens from glucose, via the benchtop centrifuge (at maximum speed for 2 rain) and the cleared enzymes myo-inositol-oxygen oxidoreductase, D,glucuronate lysates were then stored on ice and assayed immediately for the enreductase, L-gulonate NAD+-3-oxidoreductase and L-iditolzyme of interest. If crude lysates failed to demonstrate significant NAD+-5-oxidoreductase, which have been found in the mammaenzyme activity, samples of lysate were separated by gel-filtration lian lens for the first time. Glucuronate reductase has been chromatography on a Pharmacia Hi Prep Sephacryl S-300 column purified and was inhibited by thiol quenching reagents. UDPand fractions in the predicted molecular weight range of the enzyme glucuronyl transferase is also present in mammalian lenses; this of interest were then assayed individually.enzyme may be an anti-toxic defense mechanism in the lens. Enzyme assaysAll substrates and buffer components, other than those specified Key words." Gulonate; myo-Inositol; Glucuronyl transferase; separately, were obtained from Sigma Biochemicals. SpectrophotoXylulose; Lens; Cataract; Aging metric analysis was carried out using a Beckman DU-70 spectrophotometer with a water-heated cuvette holder. myo-Inositol-l-phosphatesynthetase, myo-Inositol-l-phosphate synthetase was assayed by a modification of the method of Eisenberg [10]. Lens lysates contain many potentially glucose-6-phos-1. Introduction phate-utilising enzymes and addition of labeled G-6-P to a crude lens lysate would therefore yield a large number of different labeled prodXylose-fed young rats accumulate polyols, including xylitol ucts, making it difficult to identify any inositol-l-phosphate produced, myo-Inositol-phosphate synthetase has been reported in [1] and develop cataractous lesions. Kinoshita and colleagues non-lens tissues as having a molecular mass of approx. 215 kDa have proposed that 'sugar' cataract arises through osmotic [10]. HPLC gel filtration was used to isolate fractions of lens lysate damage to the lens as a direct result of polyol accumulation corresponding to that molecular mass range and those fractions were [2,3]. However, whilst xylose-fed adult rats accumulate similar then pooled and assayed for myo-inositol-l-phosphate synthetase acpolyol levels to young rats, they fail to develop cataract sugtivity. Incubations were carried out in 50 mM sodium phosphate buffer containing 1 mM NAD +, 1 mM unlabeled G-6-P and 0.1 gesting that the relationship between polyol levels...

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“…molecular weight crystallins in human lens, and it is well known that these molecules are either degraded or become crosslinked in cataract (Harding & Crabbe, 1984). Using the computer graphics program FRODO (Jones, 1978), bovine yS-crystallin has already been modeled based on the coordinates of bovine yB-crystallin (Quax-Jeuken et al, 1985).…”

mentioning

confidence: 99%

Three‐dimensional model and quaternary structure of the human eye lens protein γS‐crystallin based on β‐ and γ‐crystallin X‐ray coordinates and ultracentrifugation

et al. 1994

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A 3-dimensional model of the human eye lens protein yS-crystallin has been constructed using comparative modeling approaches encoded in the program COMPOSER on the basis of the 3-dimensional structure of y-crystallin and 0-crystallin. The model is biased toward the monomeric yB-crystallin, which is more similar in sequence. Bovine yS-crystallin was shown to be monomeric by analytical ultracentrifugation without any tendency to form assemblies up to concentrations in the millimolar range. The connecting peptide between domains was therefore built assuming an intramolecular association as in the monomeric y-crystallins. Because the linker has 1 extra residue compared with yB and PB2, the conformation of the connecting peptide was constructed by using a fragment from a protein database. yS-crystallin differs from yB-crystallin mainly in the interface region between domains. The charged residues are generally paired, although in a different way from both 0-and y-crystallins, and may contribute to the different roles of these proteins in the lens.

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The Lens: Development, Proteins, Metabolism and Cataract

Cited by 221 publications

References 1,511 publications

Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses and aged human lenses

Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses and aged human lenses

Accumulation of xylitol in the mammalian lens is related to glucuronate metabolism

Three‐dimensional model and quaternary structure of the human eye lens protein γS‐crystallin based on β‐ and γ‐crystallin X‐ray coordinates and ultracentrifugation

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