Spatial distribution of metabolites in the human lens

Tamara, Sem; Yanshole, Lyudmila V.; Yanshole, Vadim V.; Fursova, Anjella Zh.; Stepakov, Denis A.; Новоселов, В. П.; Tsentalovich, Yuri P.

doi:10.1016/j.exer.2015.10.015

Cited by 16 publications

(12 citation statements)

References 30 publications

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“…One recent example has combined a microsampling approach with HPLC-MS to map the distribution of several metabolites, including GSH, UV filters and some GSH cofactors radially through the equatorial region and along the optical axis of normal and cataractous human lenses. 82 A total of thirty four metabolites were confidently identified and mapped, confirming the spatial distributions and relative concentrations of GSH and its related molecules in different lens regions, which had been reported previously using mass spectrometry analysis of more crudely dissected lenses. 83,84 Recently, imaging mass spectrometry (IMS) has emerged as a new biomedical imaging technology, which can provide the spatial distribution and relative abundance of hundreds of molecules from a thin tissue section in a single dataset.…”

Section: Visualizing Gsh Uptake and Metabolism In The Lenssupporting

confidence: 82%

“…For example, it is a simple task for mass spectrometry to distinguish between GSH and GSSG without molecular derivatisation or labelling, and to use targeted detection of other endogenous GSH conjugates based on their mass (or more specifically mass‐to‐charge ratio, m/z ). One recent example has combined a microsampling approach with HPLC‐MS to map the distribution of several metabolites, including GSH, UV filters and some GSH cofactors radially through the equatorial region and along the optical axis of normal and cataractous human lenses 82 . A total of thirty four metabolites were confidently identified and mapped, confirming the spatial distributions and relative concentrations of GSH and its related molecules in different lens regions, which had been reported previously using mass spectrometry analysis of more crudely dissected lenses 83,84 …”

Section: Visualizing Gsh Uptake and Metabolism In The Lensmentioning

confidence: 99%

See 1 more Smart Citation

Age‐dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation—A review

Lim

Grey

Zahraei

et al. 2020

Clinical Exper Ophthalmology

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Ocular tissues possess a robust antioxidant defence system to minimize oxidative stress and preserve tissue structure and function. Glutathione (GSH) is a powerful antioxidant and in the lens exists at unusually high concentrations. However, with advancing age, GSH levels deplete specifically in the lens centre initiating a chain of biochemical events that ultimately result in protein aggregation, light scattering and age-related nuclear cataract. However, antioxidant supplementation has been shown to be ineffective in preventing or delaying cataract indicating that a better understanding of the delivery, uptake and metabolism of GSH in the different regions of the lens is required. This information is essential for the development of scientifically informed approaches that target the delivery of GSH to the lens nucleus, the region of the lens most affected by age-related cataract.

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Section: Visualizing Gsh Uptake and Metabolism In The Lenssupporting

confidence: 82%

Section: Visualizing Gsh Uptake and Metabolism In The Lensmentioning

confidence: 99%

Age‐dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation—A review

Lim

Grey

Zahraei

et al. 2020

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

show abstract

“…The mass spectra were recorded in a positive mode with 50–1000 m/z range. The MS setup, the calibration procedure, and the data processing were described in detail earlier [25,26,27,51]. Briefly, eight solutions containing an equimolar mixture of 26 metabolites with the concentrations ranging from 43.5 to 87 μM were subjected to LC-MS, and the calibration curves for each metabolite were plotted.…”

Section: Methodsmentioning

confidence: 99%

Seasonal Variations and Interspecific Differences in Metabolomes of Freshwater Fish Tissues: Quantitative Metabolomic Profiles of Lenses and Gills

Tsentalovich

Yanshole

et al. 2019

Metabolites

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This work represents the first comprehensive report on quantitative metabolomic composition of tissues of pike-perch (Sander lucioperca) and Siberian roach (Rutilus rutilus lacustris). The total of 68 most abundant metabolites are identified and quantified in the fish lenses and gills by the combination of LC-MS and NMR. It is shown that the concentrations of some compounds in the lens are much higher than that in the gills; that indicates the importance of these metabolites for the adaptation to the specific living conditions and maintaining the homeostasis of the fish lens. The lens metabolome undergoes significant seasonal changes due to the variations of dissolved oxygen level and fish feeding activity. The most season-affected metabolites are osmolytes and antioxidants, and the most affected metabolic pathway is the histidine pathway. In late autumn, the major lens osmolytes are N-acetyl-histidine and threonine phosphoethanolamine (Thr-PETA), while in winter the highest concentrations were observed for serine phosphoethanolamine (Ser-PETA) and myo-inositol. The presence of Thr-PETA and Ser-PETA in fish tissues and their role in cell osmotic protection are reported for the first time. The obtained concentrations can be used as baseline levels for studying the influence of environmental factors on fish health.

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“…Recently, metabolomics has been used in both clinical and animal studies of several diseases, including some ocular pathologies [5,6]. However, metabolomic studies specifically focused on cataracts are very limited [7][8][9]. Early proteomic and RNA-seq studies that investigated the biochemical mechanisms of congenital Vision Research.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have examined the spatial distribution of metabolites in human lenses, the effect of human cataracts on metabolite levels, and the metabolic composition of the rat lens with NMR and LC-MS methods [ 5 , 7 – 9 ]. Analyzing the spatial distribution of 34 metabolites in the human lens revealed that most metabolites had a homogenous distribution [ 8 ]. Additionally, most metabolites in rat lenses exhibited a gradual decrease with age [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Alpha-crystallin mutations alter lens metabolites in mouse models of human cataracts

et al. 2020

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Cataracts are a major cause of blindness worldwide and commonly occur in individuals over 70 years old. Cataracts can also appear earlier in life due to genetic mutations. The lens proteins, αA-and αB-crystallins, are chaperone proteins that have important roles maintaining protein solubility to prevent cataract formation. Mutations in the CRYAA and CRYAB crystallin genes are associated with autosomal dominant early onset human cataracts. Although studies about the proteomic and genomic changes that occur in cataracts have been reported, metabolomics studies are very limited. Here, we directly investigated cataract metabolism using gas-chromatography-mass spectrometry (GC-MS) to analyze the metabolites in adult Cryaa-R49C and Cryab-R120G knock-in mouse lenses. The most abundant metabolites were myo-inositol, L-(+)-lactic acid, cholesterol, phosphate, glycerol phosphate, palmitic and 9-octadecenoic acids, α-D-mannopyranose, and β-D-glucopyranose. Cryaa-R49C knock-in mouse lenses had a significant decrease in the number of sugars and minor sterols, which occurred in concert with an increase in lactic acid. Cholesterol composition was unchanged. In contrast, Cryab-R120G knock-in lenses exhibited increased total amino acid content including valine, alanine, serine, leucine, isoleucine, glycine, and aspartic acid. Minor sterols, including cholest-7-en-3-ol and glycerol phosphate were decreased. These studies indicate that lenses from Cryaa-R49C and Cryab-R120G knock-in mice, which are models for human cataracts, have unique amino acid and metabolite profiles.

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Spatial distribution of metabolites in the human lens

Cited by 16 publications

References 30 publications

Age‐dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation—A review

Age‐dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation—A review

Seasonal Variations and Interspecific Differences in Metabolomes of Freshwater Fish Tissues: Quantitative Metabolomic Profiles of Lenses and Gills

Alpha-crystallin mutations alter lens metabolites in mouse models of human cataracts

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