Calbiague-Garcia Victor, Chen Yiyi, Cádiz Bárbara, Tapia Felipe, Paquet-Durand François, Schmachtenberg Oliver
PhD Program in Neuroscience, Universidad de Valparaíso, Valparaíso, Chile; CINV, Instituto de Biología, Universidad de Valparaíso, Valparaíso, Chile.
Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
J Biol Chem. 2024 Apr;300(4):106794. doi: 10.1016/j.jbc.2024.106794. Epub 2024 Feb 24.
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.
视网膜双极细胞和无长突细胞从光感受器接收视觉信息,并参与视网膜图像处理的第一步。几项研究表明,由于在有氧条件下这种代谢物的高产量,视网膜中存在有氧糖酵解和乳酸穿梭系统。然而,双极细胞是否构成这个代谢回路的一部分仍不清楚。在这里,我们表明单羧酸转运体2在内视网膜神经元中表达并具有功能。此外,我们使用基因编码的FRET纳米传感器来证明内视网膜神经元消耗细胞外乳酸作为葡萄糖替代物的能力。在视杆双极细胞中,乳酸消耗使细胞能够维持离子和电反应的稳态。我们还发现乳酸合成和转运体抑制会导致功能改变和细胞死亡率增加。总体而言,我们的数据揭示了视网膜代谢中一个显著但仍知之甚少的方面。