Extracellular lactate as an alternative energy source for retinal bipolar cells

• Published in: The Journal of biological chemistry Vol. 300; no. 4; p. 106794
• Main Authors: Calbiague-Garcia, Victor, Chen, Yiyi, Cádiz, Bárbara, Tapia, Felipe, Paquet-Durand, François, Schmachtenberg, Oliver
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2024; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; bipolar cells; Energy Metabolism; Glucose - metabolism; lactate; lactate shuttle; Lactic Acid - metabolism; Mice; monocarboxylate transporters; Monocarboxylic Acid Transporters - genetics; Monocarboxylic Acid Transporters - metabolism; retina; Retina - cytology; Retina - metabolism; Retinal Bipolar Cells - metabolism; BC; RT; INL; RPE; Iout; LDH-A; AUC; RBC; retina; monocarboxylate transporters; MC; lactate shuttle; Δ6; AC; mTFP; PKM2; Ica; bipolar cells; DAPI; Syn; ROI; Vmemb; GFAP; ERG; lactate; MCT
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1016/j.jbc.2024.106794

Retinal bipolar and amacrine cells receive visual information from photoreceptors and participate in the first steps of image processing in the retina. Several studies have suggested the operation of aerobic glycolysis and a lactate shuttle system in the retina due to the high production of this metabolite under aerobic conditions. However, whether bipolar cells form part of this metabolic circuit remains unclear. Here, we show that the monocarboxylate transporter 2 is expressed and functional in inner retinal neurons. Additionally, we used genetically encoded FRET nanosensors to demonstrate the ability of inner retinal neurons to consume extracellular lactate as an alternative to glucose. In rod bipolar cells, lactate consumption allowed cells to maintain the homeostasis of ions and electrical responses. We also found that lactate synthesis and transporter inhibition caused functional alterations and an increased rate of cell death. Overall, our data shed light on a notable but still poorly understood aspect of retinal metabolism.