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Rupali Vohra, Dorte Marie Skytt, Blanca I Aldana, Kristine Freude, Helle Waagepetersen, Linda Hildegaard Bergersen, Miriam Kolko; Müller cell survival and function is maintained by the presence of lactate. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1480.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effect of lactate exposure on Müller cell survival and function.
The human Müller cell line MIO-M1 and primary mice Müller cells were incubated with or without 6 mM glucose for 2 and 24 hours. Moreover, cultures were exposed to 10 mM or 20 mM L-lactate, respectively. Lactate transport by monocarboxylate transporters was blocked by 4-cinnamic acid and D-lactate. Cell survival was assessed through MTT. Glycogen and ATP contents were measured by commercial assays. Müller cell function was evaluated through the Müller cells’ ability to take up glutamate.
Both 10 mM and 20 mM of L-Lactate exposure increased Müller cell survival independently of the presence of glucose. This effect was abolished by the addition of 4-cinnamic acid to the treatment media, whereas survival continued to increase in response to addition of D-lactate in the treatment media during glucose deprivation. 10 mM L-Lactate exposure prevented complete glycogen depletion in MIO-M1 cells. Furthermore, ATP levels decreased over time in MIO-M1 cells and remained stable over time in primary Müller cells. Glutamate uptake increased after 2 hours and decreased after 24 hours in glucose restricted Müller cells compared to cells with sufficient glucose availability. The addition of treatment with 10 mM L-lactate increased glutamate uptake in both glucose supplemented and glucose restricted cells.
Lactate is a key component in Müller cell survival and function. Since Müller cells are pivotal in the prevention of retinal ganglion cell death, lactate and its receptor-mediated pathways may ultimately be novel targets to prevent glaucomatous neurodegeneration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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