Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark.
Faculty of Health and Medical Sciences, Department of Veterinary and Animal Sciences, Section for Anatomy & Biochemistry, University of Copenhagen, Grønnegårdsvej 7, 1870, Frederiksberg C, Denmark.
Mol Neurobiol. 2018 Dec;55(12):9108-9121. doi: 10.1007/s12035-018-1056-2. Epub 2018 Apr 11.
Müller cells are pivotal in sustaining retinal ganglion cells, and an intact energy metabolism is essential for upholding Müller cell functions. The present study aimed to investigate the impact of lactate on Müller cell survival and function. Primary mice Müller cells and human Müller cell lines (MIO-M1) were treated with or without lactate (10 or 20 mM) for 2 and 24 hours. Simultaneously, Müller cells were incubated with or without 6 mM of glucose. L-lactate exposure increased Müller cell survival independently of the presence of glucose. This effect was abolished by the addition of the monocarboxylate inhibitor 4-cinnamic acid to the treatment media, whereas survival continued to increase in response to addition of D-lactate during glucose restriction. ATP levels decreased over time in MIO-M1 cells and remained stable over time in primary Müller cells. Lactate was preferably metabolized in MIO-M1 cells compared to glucose, and 10 mM of L-Lactate exposure prevented complete glycogen depletion in MIO-M1 cells. Glutamate uptake increased after 2 hours and decreased after 24 hours in glucose-restricted Müller cells compared to cells with glucose supplement. The addition of 10 mM of lactate to the treatment media increased glutamate uptake in glucose supplemented and restricted cells. In conclusion, lactate is a key component in maintaining Müller cell survival and function. Hence, lactate administration may be of great future interest, ultimately leading to novel therapies to rescue retinal ganglion cells.
Müller 细胞在维持视网膜神经节细胞方面起着关键作用，而完整的能量代谢对于维持 Müller 细胞功能至关重要。本研究旨在探讨乳酸对 Müller 细胞存活和功能的影响。用或不用乳酸（10 或 20mM）处理原代小鼠 Müller 细胞和人 Müller 细胞系（MIO-M1）2 和 24 小时。同时，用或不用 6mM 的葡萄糖孵育 Müller 细胞。L-乳酸暴露可独立于葡萄糖的存在增加 Müller 细胞的存活率。这种作用被添加到处理培养基中的单羧酸抑制剂 4-肉桂酸所消除，而在葡萄糖限制时添加 D-乳酸，存活率继续增加。MIO-M1 细胞中的 ATP 水平随时间推移而降低，而原代 Müller 细胞中的 ATP 水平随时间推移而稳定。与葡萄糖相比，MIO-M1 细胞中乳酸优先代谢，10mM 的 L-乳酸暴露可防止 MIO-M1 细胞中糖原完全耗尽。与有葡萄糖补充的细胞相比，葡萄糖限制的 Müller 细胞中的谷氨酸摄取在 2 小时后增加，在 24 小时后减少。在治疗培养基中添加 10mM 的乳酸可增加葡萄糖补充和限制细胞中的谷氨酸摄取。总之，乳酸是维持 Müller 细胞存活和功能的关键组成部分。因此，乳酸的给药可能具有很大的未来意义，最终导致新的治疗方法来挽救视网膜神经节细胞。
