Abstract

Here we report multiple lines of evidence for a comprehensive model of energy metabolism in the vertebrate eye. Metabolic flux, locations of key enzymes, and our finding that glucose enters mouse and zebrafish retinas mostly through photoreceptors support a conceptually new model for retinal metabolism. In this model, glucose from the choroidal blood passes through the retinal pigment epithelium to the retina where photoreceptors convert it to lactate. Photoreceptors then export the lactate as fuel for the retinal pigment epithelium and for neighboring Müller glial cells. We used human retinal epithelial cells to show that lactate can suppress consumption of glucose by the retinal pigment epithelium. Suppression of glucose consumption in the retinal pigment epithelium can increase the amount of glucose that reaches the retina. This framework for understanding metabolic relationships in the vertebrate retina provides new insights into the underlying causes of retinal disease and age-related vision loss.

Article and author information

Author details

  1. Mark A Kanow

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michelle M Giarmarco

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3344-4268
  3. Connor SR Jankowski

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kristine Tsantilas

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Abbi L Engel

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jianhai Du

    Department of Ophthalmology, West Virginia University, Morgantown, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jonathan D Linton

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Christopher C Farnsworth

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Stephanie R Sloat

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Austin Rountree

    Department of Medicine, UW Diabetes Institute, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Ian R Sweet

    Department of Medicine, UW Diabetes Institute, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Ken J Lindsay

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Edward D Parker

    Department of Ophthalmology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Susan E Brockerhoff

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Martin Sadilek

    Department of Chemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Jennifer R Chao

    Department of Ophthalmology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6859-5552
  17. James B Hurley

    Department of Biochemistry, University of Washington, Seattle, United States
    For correspondence
    jbhhh@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7754-0705

Funding

National Eye Institute (EY06641)

  • James B Hurley

National Eye Institute (EY017863)

  • James B Hurley

National Eye Institute (EY026030)

  • Jianhai Du
  • Jennifer R Chao

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

Reviewing Editor

  1. Ralph DeBerardinis, UT Southwestern Medical Center, United States

Ethics

Animal experimentation: All animal research was authorized by the University of Washington Institutional Animal Care and Use Committee.

Version history

  1. Received: May 22, 2017
  2. Accepted: September 12, 2017
  3. Accepted Manuscript published: September 13, 2017 (version 1)
  4. Version of Record published: September 27, 2017 (version 2)

Copyright

© 2017, Kanow 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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  1. Mark A Kanow
  2. Michelle M Giarmarco
  3. Connor SR Jankowski
  4. Kristine Tsantilas
  5. Abbi L Engel
  6. Jianhai Du
  7. Jonathan D Linton
  8. Christopher C Farnsworth
  9. Stephanie R Sloat
  10. Austin Rountree
  11. Ian R Sweet
  12. Ken J Lindsay
  13. Edward D Parker
  14. Susan E Brockerhoff
  15. Martin Sadilek
  16. Jennifer R Chao
  17. James B Hurley
(2017)
Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
eLife 6:e28899.
https://doi.org/10.7554/eLife.28899

Share this article

https://doi.org/10.7554/eLife.28899

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