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Essential Roles of Lactate in Müller Cell Survival and Function

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  1. Lactate: More Than Merely a Metabolic Waste Product in the Inner Retina

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  1. Lactate: More Than Merely a Metabolic Waste Product in the Inner Retina

    Research output: Contribution to journalReviewResearchpeer-review

  2. Melanopsin-mediated pupillary light reflex and sleep quality in patients with normal tension glaucoma

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  3. Lactate-Mediated Protection of Retinal Ganglion Cells

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  4. Dual Properties of Lactate in Müller Cells: The Effect of GPR81 Activation

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  5. Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation

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  • Rupali Vohra
  • Blanca I Aldana
  • Dorte M Skytt
  • Kristine Freude
  • Helle Waagepetersen
  • Linda H Bergersen
  • Miriam Kolko
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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.

Original languageEnglish
JournalMolecular Neurobiology
Volume55
Issue number12
Pages (from-to)9108-9121
Number of pages14
ISSN0893-7648
DOIs
Publication statusPublished - 2018

    Research areas

  • Adenosine Triphosphate/metabolism, Animals, Cell Survival/drug effects, Cells, Cultured, Ependymoglial Cells/cytology, Glucose/metabolism, Glutamic Acid/metabolism, Glycogen/metabolism, Lactic Acid/metabolism, Mice, Inbred C57BL, Monocarboxylic Acid Transporters/metabolism, Time Factors

ID: 56564650