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Quantitative metabolomic analysis of changes in the lens and aqueous humor under development of age-related nuclear cataract

Metabolomics volume 15, Article number: 29 (2019) Cite this article

Abstract

Introduction

Metabolites are essential for the proper functioning of the eye lens, they either enter the lens from the aqueous humor (AH), or are synthesized in the lens epithelium. Antioxidants, osmolytes and UV filters are especially important for the lens protection, and their lack may cause the development of ophthalmic diseases.

Objectives

Comparison of the metabolomic compositions of lenses and AH taken from cataract patients with that taken from human cadavers without cataract can shed light onto molecular mechanisms underlying onset of age-related nuclear cataract.

Methods

Combined use of 1H nuclear magnetic resonance and high performance liquid chromatography with optical and high-resolution mass spectrometric detection for the identification and quantification of metabolites in the lens and AH extracts.

Results

The concentrations of 86 metabolites were determined for four groups of samples, including lenses and AH from cataract patients and from human cadavers. In cataractous lens the most abundant metabolites are (in descending order): myo-inositol, lactate, acetate, glutamate, glutathione; in AH—lactate, glucose, glutamine, alanine, valine. The concentrations of the majority of metabolites in normal post-mortem samples of both lens and AH are higher than that in samples from the cataract patients.

Conclusions

Comparison of metabolite concentrations in lens and corresponding AH reveal that the most important for the lens protection metabolites are synthesized in the lens epithelial cells. The reduced levels of antioxidants, UV filters, and osmolytes were found in the cataractous lenses what cannot be explained by post-mortem changes in normal lens; that indicates that the age-related nuclear cataract development may originate from the dysfunction of the lens epithelial cells.

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Acknowledgements

The authors thank Denis A. Stepakov and Vladimir P. Novoselov from Novosibirsk Regional Clinical Bureau of Forensic Medicine for the collection of post-mortem samples and Anjella Zh. Fursova from Novosibirsk Regional Hospital for the collection of cataract samples, and Arsenty D. Melnikov for the statistical data analysis.

Funding

This work was supported by RFBR (Project 18-33-20097) in LC–MS measurements, RFBR and the government of the Novosibirsk region (Project 18-415-543006) in sample preparation, by the RFBR (Project 18-34-00137) in NMR measurements, and by the RSF (Project No. 18-73-10014) in optical measurements.

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Affiliations

  1. International Tomography Center SB RAS, Institutskaya 3a, Novosibirsk, Russia, 630090

    Vadim V. Yanshole, Lyudmila V. Yanshole, Olga A. Snytnikova & Yuri P. Tsentalovich

  2. Novosibirsk State University, Pirogova 2, Novosibirsk, Russia, 630090

    Vadim V. Yanshole, Lyudmila V. Yanshole, Olga A. Snytnikova & Yuri P. Tsentalovich

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  1. Vadim V. Yanshole
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  2. Lyudmila V. Yanshole
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  3. Olga A. Snytnikova
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  4. Yuri P. Tsentalovich
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Contributions

VY, LY, OS performed the experiments and collected the data. VY and YT designed the experiments, analyzed the data and wrote the manuscript.

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Correspondence to Vadim V. Yanshole.

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Yanshole, V.V., Yanshole, L.V., Snytnikova, O.A. et al. Quantitative metabolomic analysis of changes in the lens and aqueous humor under development of age-related nuclear cataract. Metabolomics 15, 29 (2019). https://doi.org/10.1007/s11306-019-1495-4

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  • DOI: https://doi.org/10.1007/s11306-019-1495-4

Keywords

  • Quantitative metabolomics
  • Age-related nuclear cataract
  • Mass spectrometry
  • NMR spectroscopy