Next Article in Journal
Metabolic and Molecular Basis of Sarcopenia: Implications in the Management of Urothelial Carcinoma
Next Article in Special Issue
Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium-Role in Dead Cell Clearance and Inflammation
Previous Article in Journal
Insulin and Insulin Receptors in Adipose Tissue Development
Previous Article in Special Issue
Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration
Review

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.
Int. J. Mol. Sci. 2019, 20(3), 762; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030762
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))
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
Show Figures

Graphical abstract

MDPI and ACS Style

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. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030762

AMA Style

Léveillard T, Philp NJ, Sennlaub F. Is Retinal Metabolic Dysfunction at the Center of the Pathogenesis of Age-related Macular Degeneration? International Journal of Molecular Sciences. 2019; 20(3):762. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030762

Chicago/Turabian Style

Léveillard, Thierry, Nancy J. Philp, and Florian Sennlaub. 2019. "Is Retinal Metabolic Dysfunction at the Center of the Pathogenesis of Age-related Macular Degeneration?" International Journal of Molecular Sciences 20, no. 3: 762. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030762

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop