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Int. J. Mol. Sci. 2019, 20(3), 762; https://doi.org/10.3390/ijms20030762

Is Retinal Metabolic Dysfunction at the Center of the Pathogenesis of Age-related Macular Degeneration?

1
. Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012 Paris, France
2
. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
3
. Department of Therapeutics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012 Paris, France
*
Author to whom correspondence should be addressed.
Received: 21 December 2018 / Revised: 4 February 2019 / Accepted: 5 February 2019 / Published: 11 February 2019
(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD))
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Abstract

The retinal pigment epithelium (RPE) forms the outer blood–retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized via OXPHOS. Excess lactate in the RPE is transported across the basolateral membrane to the choroid. The uptake of glucose by cone photoreceptor cells is enhanced by rod-derived cone viability factor (RdCVF) secreted by rods and by insulin signaling. Together, the three cells act as symbiotes: the RPE supplies the glucose from the choroidal circulation to the photoreceptors, the rods help the cones, and both produce lactate to feed the RPE. In age-related macular degeneration this delicate ménage à trois is disturbed by the chronic infiltration of inflammatory macrophages. These immune cells also rely on aerobic glycolysis and compete for glucose and produce lactate. We here review the glucose metabolism in the homeostasis of the outer retina and in macrophages and hypothesize what happens when the metabolism of photoreceptors and the RPE is disturbed by chronic inflammation. View Full-Text
Keywords: cone photoreceptor; inflammatory macrophage; aerobic glycolysis; lactate transporter; retinal degeneration; rod-derived cone viability factor cone photoreceptor; inflammatory macrophage; aerobic glycolysis; lactate transporter; retinal degeneration; rod-derived cone viability factor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Léveillard, T.; Philp, N.J.; Sennlaub, F. Is Retinal Metabolic Dysfunction at the Center of the Pathogenesis of Age-related Macular Degeneration? Int. J. Mol. Sci. 2019, 20, 762.

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