Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye

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 metabol...

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Main Authors: Mark A Kanow, Michelle M Giarmarco, Connor SR Jankowski, Kristine Tsantilas, Abbi L Engel, Jianhai Du, Jonathan D Linton, Christopher C Farnsworth, Stephanie R Sloat, Austin Rountree, Ian R Sweet, Ken J Lindsay, Edward D Parker, Susan E Brockerhoff, Martin Sadilek, Jennifer R Chao, James B Hurley
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/28899
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author Mark A Kanow
Michelle M Giarmarco
Connor SR Jankowski
Kristine Tsantilas
Abbi L Engel
Jianhai Du
Jonathan D Linton
Christopher C Farnsworth
Stephanie R Sloat
Austin Rountree
Ian R Sweet
Ken J Lindsay
Edward D Parker
Susan E Brockerhoff
Martin Sadilek
Jennifer R Chao
James B Hurley
author_facet Mark A Kanow
Michelle M Giarmarco
Connor SR Jankowski
Kristine Tsantilas
Abbi L Engel
Jianhai Du
Jonathan D Linton
Christopher C Farnsworth
Stephanie R Sloat
Austin Rountree
Ian R Sweet
Ken J Lindsay
Edward D Parker
Susan E Brockerhoff
Martin Sadilek
Jennifer R Chao
James B Hurley
author_sort Mark A Kanow
collection DOAJ
description 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.
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spelling doaj.art-aff27e94dd9b414d9153404c6b6c95512022-12-22T03:52:39ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.28899Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eyeMark A Kanow0Michelle M Giarmarco1https://orcid.org/0000-0003-3344-4268Connor SR Jankowski2Kristine Tsantilas3Abbi L Engel4Jianhai Du5Jonathan D Linton6Christopher C Farnsworth7Stephanie R Sloat8Austin Rountree9Ian R Sweet10Ken J Lindsay11Edward D Parker12Susan E Brockerhoff13Martin Sadilek14Jennifer R Chao15https://orcid.org/0000-0002-6859-5552James B Hurley16https://orcid.org/0000-0002-7754-0705Department of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Ophthalmology, University of Washington, Seattle, United StatesDepartment of Ophthalmology, West Virginia University, Morgantown, United States; Department of Biochemistry, West Virginia University, Morgantown, United StatesDepartment of Biochemistry, University of Washington, Seattle, United States; Department of Ophthalmology, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Medicine, UW Diabetes Institute, University of Washington, Seattle, United StatesDepartment of Medicine, UW Diabetes Institute, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United States; Fred Hutchinson Cancer Research Center, Seattle, United StatesDepartment of Ophthalmology, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United States; Department of Ophthalmology, University of Washington, Seattle, United StatesDepartment of Chemistry, University of Washington, Seattle, United StatesDepartment of Ophthalmology, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United States; Department of Ophthalmology, University of Washington, Seattle, United StatesHere 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.https://elifesciences.org/articles/28899retinaenergy metabolismphotoreceptors
spellingShingle Mark A Kanow
Michelle M Giarmarco
Connor SR Jankowski
Kristine Tsantilas
Abbi L Engel
Jianhai Du
Jonathan D Linton
Christopher C Farnsworth
Stephanie R Sloat
Austin Rountree
Ian R Sweet
Ken J Lindsay
Edward D Parker
Susan E Brockerhoff
Martin Sadilek
Jennifer R Chao
James B Hurley
Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
eLife
retina
energy metabolism
photoreceptors
title Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
title_full Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
title_fullStr Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
title_full_unstemmed Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
title_short Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
title_sort biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
topic retina
energy metabolism
photoreceptors
url https://elifesciences.org/articles/28899
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