Müller cell survival and function is maintained by the presence of lactate

Abstract

Purpose : To evaluate the effect of lactate exposure on Müller cell survival and function.

Methods : 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.

Results : 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.

Conclusions : 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.