Cited by 381Retinal Development and DisordersRetinal Diseases and TreatmentsRetinal Imaging and Analysis

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

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Kanow, Mark A, Giarmarco, Michelle M, Jankowski, Connor SR, Tsantilas, Kristine, Engel, Abbi L, Du, Jianhai, Linton, Jonathan D, Farnsworth, Christopher C, Sloat, Stephanie R, Rountree, Austin, Sweet, Ian R, Lindsay, Ken J, Parker, Edward D, Brockerhoff, Susan E, Sadilek, Martin, Chao, Jennifer R, Hurley, James B·2017·eLife

DOI 10.7554/elife.28899PMC PMC5617631

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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.

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Additional file 7 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
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Additional file 8 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
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Additional file 2 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
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Additional file 4 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
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Additional file 6 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
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Additional file 1 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
Todorova, V., Stauffacher, M. F., Ravotto, L., Nötzli, S., Karademir, D., Ebner, L. J. A., Imsand, C., Merolla, L., Hauck, S. M., Samardzija, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26573401
Additional file 5 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
Todorova, V., Stauffacher, M. F., Ravotto, L., Nötzli, S., Karademir, D., Ebner, L. J. A., Imsand, C., Merolla, L., Hauck, S. M., Samardzija, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26573413
Additional file 3 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
Todorova, V., Stauffacher, M. F., Ravotto, L., Nötzli, S., Karademir, D., Ebner, L. J. A., Imsand, C., Merolla, L., Hauck, S. M., Samardzija, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26573407
Additional file 9 of Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
Todorova, V., Stauffacher, M. F., Ravotto, L., Nötzli, S., Karademir, D., Ebner, L. J. A., Imsand, C., Merolla, L., Hauck, S. M., Samardzija, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26573425
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Authors: Kanow, M. A., Giarmarco, M. M., Jankowski, C. S., Tsantilas, K., Engel, A. L., Du, J., Linton, J. D., Farnsworth, C. C., Sloat, S. R., Rountree, A., Sweet, I. R., Lindsay, K. J., Parker, E. D., Brockerhoff, S. E., Sadilek, M., Chao, J. R., & Hurley, J. B.
Affiliations: University of Washington (US)
West Virginia University (US)
Department of Chemistry, University of Washington, Seattle, United States
Corresponding author: Hurley, James B
ORCID: Giarmarco, Michelle M
Jankowski, Connor SR
Tsantilas, Kristine
Engel, Abbi L
Du, Jianhai
Sweet, Ian R
Brockerhoff, Susan E
Chao, Jennifer R
Hurley, James B
Venue: eLife
Publisher: eLife Sciences Publications, Ltd
Published: 2017-09-13
Volume: 6
ISSN: 2050-084X (ISSN-L)
DOI: 10.7554/elife.28899
PMC: PMC5617631
OpenAlex: W2617421506
Cited by: 377
References: 64
Citations by year: 2026: 44 · 2025: 36 · 2024: 59 · 2023: 48 · 2022: 48 · 2021: 53 · 2020: 48 · 2019: 23 · 2018: 15 · 2017: 2
FWCI: 9.83
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
creativecommons.org/licenses/by/4.0/ (am)
creativecommons.org/licenses/by/4.0/ (tdm)
Locations: eLife (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
The Research Repository @ WVU (West Virginia University) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Science Foundation (GRFP 2013158531)
National Eye Institute (5T32EY007031, EY026030, EY026020, EY06641, EY017863, EY001730)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 17047)
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords: retinal metabolism, retinal pigment epithelium, photoreceptors, lactate, glucose metabolism, Müller cells, choroid, metabolic flux, age-related vision loss, retinal disease, mice, zebrafish
MeSH terms: Adaptation, Ocular, Animals, Energy Metabolism, Glucose, Humans, Lactates, Photoreceptor Cells, Zebrafish, Mice, Retinal Pigment Epithelium, Ependymoglial Cells

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

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