Two‐photon AMPK and ATP imaging reveals the bias between rods and cones in glycolysis utility

In vertebrates, retinal rod and cone photoreceptor cells rely significantly on glycolysis. Lactate released from fuels neighboring pigment epithelium Müller glial through oxidative phosphorylation. To understand this highly heterogeneous metabolic environment around cells, single-cell analysis is needed. Here, we visualized cellular AMP-activated protein kinase (AMPK) activity ATP levels in the retina by two-photon microscopy. Transgenic mice expressing a hyBRET-AMPK biosensor were used for measuring AMPK activity. GO-ATeam2 transgenic level. Temporal responses successfully detected live explants upon drug perfusion. A glycolysis inhibitor, 2-deoxy-d-glucose (2-DG), activated reduced ATP. These effects clearly stronger rods than cones. Notably, started to recover at 30 min onset of 2-DG Consistent with these findings, ex vivo electroretinogram recordings showed transient slowdown dim flash during 60-min perfusion, whereas not affected. Based results, propose that cones surrounded glycolytic become less dependent glycolysis, also within 60 inhibition.