Lactate-Mediated Protection of Retinal Ganglion Cells
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Lactate-Mediated Protection of Retinal Ganglion Cells. / Vohra, Rupali; Aldana, Blanca I.; Bulli, Giorgia; Skytt, Dorte M.; Waagepetersen, Helle; Bergersen, Linda H.; Kolko, Miriam.
In: Journal of Molecular Biology, Vol. 431, No. 9, 19.04.2019, p. 1878-1888.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Lactate-Mediated Protection of Retinal Ganglion Cells
AU - Vohra, Rupali
AU - Aldana, Blanca I.
AU - Bulli, Giorgia
AU - Skytt, Dorte M.
AU - Waagepetersen, Helle
AU - Bergersen, Linda H.
AU - Kolko, Miriam
PY - 2019/4/19
Y1 - 2019/4/19
N2 - Loss of retinal ganglion cells (RGCs) is a leading cause of blinding conditions. The purpose of this study was to evaluate the effect of extracellular L-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.
AB - Loss of retinal ganglion cells (RGCs) is a leading cause of blinding conditions. The purpose of this study was to evaluate the effect of extracellular L-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.
KW - energy metabolism
KW - lactate
KW - Müller cells
KW - retinal ganglion cells
U2 - 10.1016/j.jmb.2019.03.005
DO - 10.1016/j.jmb.2019.03.005
M3 - Journal article
C2 - 30878479
AN - SCOPUS:85063221873
VL - 431
SP - 1878
EP - 1888
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 9
ER -
ID: 216915737