Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons
4 affiliations
- 1Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952, Zurich, Switzerland.
- 2Institute of Pharmacology and Toxicology and Neuroscience Center Zurich, University and ETH Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland.
- 3Centro de Estudios Cientificos-CECs, Valdivia, Chile.
- 4Facultad de Medicina, Universidad San Sebastián, Valdivia, Chile.
Abstract
The retina metabolizes glucose into lactate, a hallmark of aerobic glycolysis known as the Warburg effect. Although evidence points to rod photoreceptors as the primary source of aerobic glycolysis, a comparison of the energy metabolism in different retinal neurons has yet to be performed. We combined two-photon fluorescence lifetime imaging of biosensors with pharmacological protocols to analyze metabolic dynamics in healthy and diseased rod photoreceptors and RBPMS-positive ganglion and calretinin-positive amacrine cells. Our data reveal distinct metabolic profiles among retinal neurons, identify rods as the drivers of aerobic glycolysis, demonstrate that inner retinal neurons rely on oxidative phosphorylation, show that rods need both glycolysis and oxidative phosphorylation to maintain ATP levels, and suggest that rods can metabolize lactate. A mutation causing retinitis pigmentosa increases lactate production in rods but changes the energy metabolism only subtly otherwise. Our results improve the understanding of retinal physiology and are relevant for pathologies involving imbalanced energy metabolism.
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BibTeX
@article{wogenstein2026photoreceptors,
title = {{Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons}},
author = {Gabriele M. Wögenstein and Luca Ravotto and Vyara Todorova and Rachel M. Meister and Marijana Samardzija and L. Felipe Barros and Bruno Weber and Christian Grimm},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeg8687},
url = {https://www.science.org/doi/10.1126/sciadv.aeg8687},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons
AU - Gabriele M. Wögenstein
AU - Luca Ravotto
AU - Vyara Todorova
AU - Rachel M. Meister
AU - Marijana Samardzija
AU - L. Felipe Barros
AU - Bruno Weber
AU - Christian Grimm
PY - 2026
DA - 2026/10/09
JO - Science Advances
DO - 10.1126/sciadv.aeg8687
UR - https://www.science.org/doi/10.1126/sciadv.aeg8687
AB - The retina metabolizes glucose into lactate, a hallmark of aerobic glycolysis known as the Warburg effect. Although evidence points to rod photoreceptors as the primary source of aerobic glycolysis, a comparison of the energy metabolism in different retinal neurons has yet to be performed. We combined two-photon fluorescence lifetime imaging of biosensors with pharmacological protocols to analyze metabolic dynamics in healthy and diseased rod photoreceptors and RBPMS-positive ganglion and calretinin-positive amacrine cells. Our data reveal distinct metabolic profiles among retinal neurons, identify rods as the drivers of aerobic glycolysis, demonstrate that inner retinal neurons rely on oxidative phosphorylation, show that rods need both glycolysis and oxidative phosphorylation to maintain ATP levels, and suggest that rods can metabolize lactate. A mutation causing retinitis pigmentosa increases lactate production in rods but changes the energy metabolism only subtly otherwise. Our results improve the understanding of retinal physiology and are relevant for pathologies involving imbalanced energy metabolism.
SN - 2375-2548
ER -