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Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation

Junhua Wang, Peter D. Westenskow, Mingliang Fang, Martin Friedlander, Gary Siuzdak
Published 19 September 2016.DOI: 10.1098/rsta.2015.0376
Junhua Wang
Center for Metabolomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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Peter D. Westenskow
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USAThe Lowy Medical Research Institute, 3366 N. Torrey Pines Court, Suite 300, La Jolla, CA 92037, USA
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Mingliang Fang
Center for Metabolomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USASchool of Civil and Environmental Engineering, Nanyang Technological University, Singapore
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Martin Friedlander
Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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  • For correspondence: friedlan@scripps.edu
Gary Siuzdak
Center for Metabolomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USADepartments of Chemistry, Molecular and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
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  • For correspondence: siuzdak@scripps.edu
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Abstract

Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic ‘fingerprint’ of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques. A number of classes of metabolites were consistently dysregulated during degeneration: vitamin A analogues, fatty acid amides, long-chain polyunsaturated fatty acids, acyl carnitines and several phospholipid species. For the first time, a distinct temporal trend of several important metabolites including DHA (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), all-trans-retinal and its toxic end-product N-retinyl-N-retinylidene-ethanolamine were observed between healthy and dystrophic retinas. In this study, metabolomics was further used to determine the temporal effects of the therapeutic intervention of grafting stem cell-derived retinal pigment epithelium (RPE) in dystrophic retinas, which significantly prevented photoreceptor atrophy in our previous studies. The result revealed that lipid levels such as phosphatidylethanolamine in eyes were restored in those animals receiving the RPE grafts. In conclusion, this study provides insight into the metabolomics of retinal degeneration, and further understanding of the efficacy of RPE transplantation.

This article is part of the themed issue ‘Quantitative mass spectrometry’.

Footnotes

  • One contribution of 19 to a theme issue ‘Quantitative mass spectrometry’.

  • Accepted February 17, 2016.
  • © 2016 The Author(s)
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28 October 2016
Volume 374, issue 2079
Philosophical Transactions of the Royal Society A: Mathematical, 				Physical and Engineering Sciences: 374 (2079)
  • Table of Contents
Theme issue ‘Quantitative mass spectrometry’ compiled and edited by Pawel Urban

Keywords

retinal degeneration
metabolomics
stem cell-derived retinal pigment epithelium
cell-based therapy
lipidomics
bioinformatics
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Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation
Junhua Wang, Peter D. Westenskow, Mingliang Fang, Martin Friedlander, Gary Siuzdak
Phil. Trans. R. Soc. A 2016 374 20150376; DOI: 10.1098/rsta.2015.0376. Published 19 September 2016
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Research article:

Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation

Junhua Wang, Peter D. Westenskow, Mingliang Fang, Martin Friedlander, Gary Siuzdak
Phil. Trans. R. Soc. A 2016 374 20150376; DOI: 10.1098/rsta.2015.0376. Published 19 September 2016

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