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

Hawse, John R.; Hejtmancik, J. F.; Horwitz, Joseph; Kantorow, Marc

doi:10.1016/j.exer.2004.04.007

Cited by 78 publications

(83 citation statements)

References 33 publications

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“…12 However, the role of CAT in ocular antioxidant protection is not fully understood, partly because of overlapping substrate specificity with cellular GPx-1. The other reason is that in SC the antioxidant genes can be markedly downregulated, 29 and the progression of SC has already been associated with decreased GPx activity, both at local and systemic level. 2,3 Furthermore, lenses of acatalasemic mice were demonstrated to be almost as efficient in degrading the H 2 O 2 ex vivo as those of the wild type, 30 indicating that CAT itself may not be of critical importance for prevention of lens oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Influence of cataract maturity on aqueous humor lipid peroxidation markers and antioxidant enzymes

Mirić¹,

Kisić²,

Zoric

et al. 2013

Eye

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Purpose The impact of cataract maturity on the aqueous humor (AH) oxidant/antioxidant balance is largely controversial. This study was aimed at assessing the relationships between cataract maturity and AH lipid peroxidation markers and enzymatic antioxidants. Patients and methods The concentrations of conjugated dienes (CD), lipofuscin-like fluorescent end-products (LLF), soluble proteins, as well as the activities of superoxide dismutase (SOD) and catalase (CAT) were measured in AH samples from nondiabetic patients with either immature (n ¼ 15) or mature (n ¼ 15) cataract. Results In the overall AH sample, the mean values of CD, LLF, SOD, and CAT were 0.160±0.024 (OD 234 ), 166±27 RFU, 24.5±7.1 U/ml, and 31.9±3.9 pmol/ml, respectively. CD was positively correlated with SOD (r ¼ 0.647; Po0.001), CAT (r ¼ À 0.394; P ¼ 0.031), and LLF (r ¼ À 0.399; P ¼ 0.029). The LLF was negatively correlated with SOD (r ¼ À 0.461; P ¼ 0.010). In samples adjusted for confounding factors, differences between immature and mature cataract groups regarding SOD, CD, LLF, and total proteins were significant (Po0.05; for all variables). The multiple logistic regression analysis identified LLF (OR ¼ 4.08; P ¼ 0.038) and SOD (OR ¼ 4.99; P ¼ 0.031) as independent predictors of cataract maturity. Conclusions These results suggest that AH lipid peroxidation markers and antioxidants may significantly depend on the cataract maturity stage.

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Section: Discussionmentioning

confidence: 99%

Influence of cataract maturity on aqueous humor lipid peroxidation markers and antioxidant enzymes

Mirić¹,

Kisić²,

Zoric

et al. 2013

Eye

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“…In this paper, we have presented a 5′-flanking DNA sequence based model with parameters for the promoter matrix, the overall level of gene expression, and the change of expression levels across the human cataractous samples. We have presented and applied our modeling in the context of gene expressions measured by microarray technology (13,15,16). We have successfully dealt with the vast amount of data generated logistically to predict the gene expression profiling associated with the particular ocular disease cataract and to show the potential benefits in ophthalmic research (16).…”

Section: Discussionmentioning

confidence: 99%

“…The microarray-based mRNA expression profiles of the selected genes, involved in the human age-related cataract, are obtained from the data published by Hawse et al (13). The logarithmic fold changes in mRNA levels are deter-mined for 14 genes, whose 5′-end flanking DNA sequence is identifiable from the GenBank (NIH, Maryland).…”

Section: Methodsmentioning

confidence: 99%

“…Using the microarraybased mRNA expression profiles reported by Hawse et al (13), we focus on 14 documented genes of lens architecture and pathology, including major structural proteins RA-crystallin and 2-crystallin. The proposed approach can also predict the stimulatory or inhibitory role by the combination of cis-acting elements that have been assumed to most dominantly regulate the mRNA expression levels (8,14).…”

Section: Introductionmentioning

confidence: 99%

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Prediction of Gene Expression Levels and the Role of Cis-Acting Elements in Age-Related Cataract by Applying a Promoter-Based Modeling Approach

Lim

Cho

2008

Biotechnol Progress

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Cataract is a dynamical process of lens opacity formation involving many inter-and intracellular regulations, as well as metabolic genes and transcription factors. Using a series of microarray-derived mRNA profiles for human cataractogenesis (Hawse et al. Mol. Vision 2003, 9, 515-537), we develop a promoter-based system-theoretic modeling to demonstrate model-driven prediction of gene expression levels and to identify the role of critical cis-acting elements. In this study, 14 key mRNA expression data from the structural and pathological molecules of age-related cataract samples are used. The first seven genes consist of structural molecules, and the second half of genes are composed of heat shock proteins, filensin, and glutathione peroxidase 3. The presented result demonstrates that mRNA expression levels of structural proteins such as crystallins can be successfully predicted from 5′ flanking regulatory DNA sequences. In addition, predicted gene expression levels of heat shock protein, -tubulin, and RA-crystallin accurately estimate the stimulatory or inhibitory role of distributed cis-acting elements, i.e., c-Myc, GATA-1, GR, NE-E, and Pit-1. Although it is difficult to predict the overall gene expression levels in cataract samples, the present study shows the potential use of promoter-based modeling and prediction of the gene expression levels for age-related cataract.

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“…Na,K-ATPase is crucial to maintain the sodium homeostasis in the lens and is therefore an object of intense investigation in human cataract research (Delamere and Tamiya, 2004). Expression levels of the multifunctional extracellular matrix protein SPARC have been shown to be increased in cataractous human lenses when compared to normal lenses (Kantorow et al, 1998;Hawse et al, 2003). Both SPARC and Na,K-ATPase α1C mRNA levels were increased in lenses of Atlantic salmon fed a low-His diet compared to a higher-His diet, where the low-His fed fish were more susceptible to cataract development (Tröβe et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Effect of plant-based feed ingredients on osmoregulation in the Atlantic salmon lens

Tröβe¹,

Rhodes

Sanderson

et al. 2010

Comparative Biochemistry and Physiology Part B: Biochemistry an

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Lenses of adult Atlantic salmon fed with a plant oil and plant protein-based diet (plant diet) were compared to lenses of fish fed a diet based on traditional marine ingredients (marine diet) with respect to biochemical composition and functionality ex vivo. After 12 months of feeding, plant diet-fed fish had smaller lenses with higher water contents and lower concentrations of histidine (His) and N-acetylhistidine (NAH) than fish fed with the marine diet. Cataract development in both dietary groups was minimal and no differences between the groups were observed. Lens fatty acid and lipid class composition differed minimally, although a significant increase in linoleic acid was observed. The lenses were examined for their ability to withstand osmotic disturbances ex vivo. Culture in hypoosmotic and hyperosmotic media led to increase and decrease of lens volume, respectively. Lenses from plant diet-fed fish were less resistant to swelling and shrinking, released less NAH into the culture medium, and accumulated His and NAH at higher rates than lenses from marine diet-fed fish. Culture in hypoosmotic medium resulted in higher cataract scores than in control and hyperosmotic medium. mRNA expression of selected genes, including glutathione peroxidase 4 and SPARC (secreted protein acidic and rich in cysteine), was affected by diet and osmotic treatment. It can be concluded that lenses of farmed Atlantic salmon are affected by the diet composition, both in biochemical composition and physiological functionality in relation to osmoregulation.

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

Cited by 78 publications

References 33 publications

Influence of cataract maturity on aqueous humor lipid peroxidation markers and antioxidant enzymes

Influence of cataract maturity on aqueous humor lipid peroxidation markers and antioxidant enzymes

Prediction of Gene Expression Levels and the Role of Cis-Acting Elements in Age-Related Cataract by Applying a Promoter-Based Modeling Approach

Effect of plant-based feed ingredients on osmoregulation in the Atlantic salmon lens

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