Essential Roles of Lactate in Müller Cell Survival and Function

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

Abstract

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.

Keywords

Lactate Müller cells Survival Metabolism MCT inhibitor Glutamate uptake 

Notes

Acknowledgements

The authors thank Laboratory Technician Charlotte Taul Brændstrup for skillful assistance to the study. The study was supported by the Michaelsen Foundation, the Velux Foundation, Denmark and Fight for Sight, Denmark.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Drug Design and PharmacologyUniversity of CopenhagenCopenhagen ØDenmark
  2. 2.Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen NDenmark
  3. 3.Center of Healthy AgingUniversity of CopenhagenCopenhagen NDenmark
  4. 4.Brain and Muscle Energy Group, Faculty of Dentistry, Department of Oral BiologyUniversity of OsloOsloNorway
  5. 5.Department of OphthalmologyCopenhagen University Hospital, Rigshospitalet-GlostrupGlostrupDenmark

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