Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye
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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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The RPE is oxidative and uses lactate produced by the photoreceptors and fatty acids from ingested OSs to fuel mitochondrial metabolism.
“In contrast, the RPE is oxidative and uses lactate produced by the photoreceptors and fatty acids from ingested OSs to fuel mitochondrial metabolism (Adijanto et al., 2014; Adijanto and Philp, 2014; Kanow et al., 2017; Reyes-Reveles et al., 2017).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Kanow et al., 2017
In the retina, photoreceptors perform aerobic glycolysis and export lactate, which is then oxidized by Müller cells.
“the opposite appears to be true: photoreceptors perform aerobic glycolysis and export lactate, which is then oxidized by Müller cells (Hurley et al., 2015; Kanow et al., 2017).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Kanow et al., 2017
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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
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-09-13
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- 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 · 2013: 1
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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