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Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the periphery

  1. Ting Zhang
  2. Ling Zhu  Is a corresponding author
  3. Michele Catherine Madigan
  4. Wei Liu
  5. Weiyong Shen
  6. Svetlana Cherepanoff
  7. Fanfan Zhou
  8. Shaoxue Zeng
  9. Jianhai Du
  10. Mark Cedric Gillies
  1. The University of Sydney, Australia
  2. Sidra Medicine, Qatar
  3. St Vincent's Hospital, Australia
  4. West Virginia University, United States
Research Article
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Cite this article as: eLife 2019;8:e43598 doi: 10.7554/eLife.43598

Abstract

The human macula is more susceptible than the peripheral retina to developing blinding conditions such as age-related macular degeneration, diabetic retinopathy. A key difference between them may be the nature of their Müller cells. We found primary cultured Müller cells from macula and peripheral retina display significant morphological and transcriptomic differences. Macular Müller cells expressed more Phosphoglycerate Dehydrogenase (PHGDH, a rate-limiting enzyme in serine synthesis) than peripheral Müller cells. The serine synthesis, glycolytic and mitochondrial function were more activated in macular than peripheral Müller cells. Serine biosynthesis is critical in defending against oxidative stress. Intracellular reactive oxygen species and glutathione levels were increased in primary cultured macular Müller cells which were more susceptible to oxidative stress after inhibition of PHGDH. Our findings indicate serine biosynthesis is a critical part of the macular defence against oxidative stress and suggest dysregulation of this pathway as a potential cause of macular pathology.

Article and author information

Author details

  1. Ting Zhang

    Save Sight Institute, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Ling Zhu

    Save Sight Institute, The University of Sydney, Sydney, Australia
    For correspondence
    ling.zhu@sydney.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0776-1630
  3. Michele Catherine Madigan

    Save Sight Institute, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Wei Liu

    Clinical Genomics Laboratory, Sidra Medicine, Doha, Qatar
    Competing interests
    The authors declare that no competing interests exist.
  5. Weiyong Shen

    Save Sight Institute, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Svetlana Cherepanoff

    Department of Anatomical Pathology, St Vincent's Hospital, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Fanfan Zhou

    Faculty of Pharmacy, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Shaoxue Zeng

    Save Sight Institute, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Jianhai Du

    Department of Ophthalmology, West Virginia University, Morgantown, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Mark Cedric Gillies

    Save Sight Institute, The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Health and Medical Research Council

  • Ling Zhu
  • Weiyong Shen
  • Mark Cedric Gillies

The Ophthalmic Research Institute of Australia

  • Ling Zhu
  • Mark Cedric Gillies

National Institutes of Health

  • Jianhai Du

Lowy Medical Research Institute

  • Ting Zhang
  • Ling Zhu
  • Weiyong Shen
  • Mark Cedric Gillies

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Human retinas were obtained from post-mortem donor eyes with ethical approval from Human Research Ethics Committee of the University of Sydney (HREC#:16/282).

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: November 15, 2018
  2. Accepted: April 8, 2019
  3. Accepted Manuscript published: April 30, 2019 (version 1)
  4. Version of Record published: May 23, 2019 (version 2)

Copyright

© 2019, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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