Lactate-Mediated Protection of Retinal Ganglion Cells.
Lactate-Mediated Protection of Retinal Ganglion Cells.
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DOI：
10.1016/j.jmb.2019.03.005
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发表时间：
2019-04
影响因子：
5.6
通讯作者：
R. Vohra;B. Aldana;G. Bulli;D. Skytt;H. Waagepetersen;L. Bergersen;M. Kolko
中科院分区：
文献类型：
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作者：
R. Vohra;B. Aldana;G. Bulli;D. Skytt;H. Waagepetersen;L. Bergersen;M. Kolko
视网膜神经节细胞（RGC）的丧失是致盲的主要原因。本研究的目的是评估细胞外乳酸对通过乳酸代谢和ATP产生促进的RGC存活的影响。我们确定乳酸作为一种首选的能源基板在小鼠RGC葡萄糖，并表明，乳酸代谢，从而增加ATP的生产是促进RGC的生存在能量危机的关键组成部分。在葡萄糖存在下乳酸被释放到细胞外环境，并在葡萄糖剥夺期间被滞留在细胞内。在存在和不存在葡萄糖的情况下，乳酸摄取和代谢均未改变。然而，ATP的生产显着下降24小时的葡萄糖剥夺和乳酸的存在下显着增加。最后，乳酸暴露2和24小时，导致增加RGC的生存在葡萄糖剥夺。总之，RGCs中乳酸的代谢途径可能对解开潜在的药物靶点具有巨大的未来兴趣，最终导致预防致盲性神经退行性疾病（例如青光眼）的新疗法。
Loss of retinal ganglion cells (RGCs) is a leading cause of blinding conditions. The purpose of this study was to evaluate the effect of extracellularl-lactate on RGC survival facilitated through lactate metabolism and ATP production. We identified lactate as a preferred energy substrate over glucose in murine RGCs and showed that lactate metabolism and consequently increased ATP production are crucial components in promoting RGC survival during energetic crisis. Lactate was released to the extracellular environment in the presence of glucose and detained intracellularly during glucose deprivation. Lactate uptake and metabolism was unaltered in the presence and absence of glucose. However, the ATP production declined significantly for 24 h of glucose deprivation and increased significantly in the presence of lactate. Finally, lactate exposure for 2 and 24 h resulted in increased RGC survival during glucose deprivation. In conclusion, the metabolic pathway of lactate in RGCs may be of great future interest to unravel potential pharmaceutical targets, ultimately leading to novel therapies in the prevention of blinding neurodegenerative diseases, for example, glaucoma.