Department of Biochemistry, University of Washington, Seattle, United States
Connor SR Jankowski
Department of Biochemistry, University of Washington, Seattle, United States
Kristine Tsantilas
Department of Biochemistry, University of Washington, Seattle, United States
Abbi L Engel
Department of Ophthalmology, University of Washington, Seattle, United States
Jianhai Du
Department of Ophthalmology, West Virginia University, Morgantown, United States; Department of Biochemistry, West Virginia University, Morgantown, United States
Jonathan D Linton
Department of Biochemistry, University of Washington, Seattle, United States; Department of Ophthalmology, University of Washington, Seattle, United States
Christopher C Farnsworth
Department of Biochemistry, University of Washington, Seattle, United States
Stephanie R Sloat
Department of Biochemistry, University of Washington, Seattle, United States
Austin Rountree
Department of Medicine, UW Diabetes Institute, University of Washington, Seattle, United States
Ian R Sweet
Department of Medicine, UW Diabetes Institute, University of Washington, Seattle, United States
Ken J Lindsay
Department of Biochemistry, University of Washington, Seattle, United States; Fred Hutchinson Cancer Research Center, Seattle, United States
Edward D Parker
Department of Ophthalmology, University of Washington, Seattle, United States
Susan E Brockerhoff
Department of Biochemistry, University of Washington, Seattle, United States; Department of Ophthalmology, University of Washington, Seattle, United States
Martin Sadilek
Department of Chemistry, University of Washington, Seattle, United States
Department of Biochemistry, University of Washington, Seattle, United States; Department of Ophthalmology, University of Washington, Seattle, United States
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.
