Lactate-Mediated Protection of Retinal Ganglion Cells

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

SN - 0022-2836

VL - 431

SP - 1878

EP - 1888

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 9

ER -