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Miriam Kolko, Anne Katrine Toft-Kehler, Rupali Vohra, Sridevi Gurubaran Iswariyaraja, Dorte Skytt; Energy deprivation alters Müller cells ability to protect retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):827.
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© ARVO (1962-2015); The Authors (2016-present)
To study the effect of energy deprivation in Müller cells ability to maintain their function as well as their ability to protect retinal ganglion cells (RGC).
The human Müller cell line, MIO-M1 and primary mouse Müller cells were used to study changes in glutamate uptake, glutamate release, excitatory amino acid transporter (EAAT) protein expression, ATP levels and glycogen content, when cells were compromised from energy. Moreover, a co-culture system of primary RGC cultures and primary Müller cells, separated by an insert, was used to evaluate the role of Müller cells in RGC survival.
EAAT1 and EAAT2 proteins were up-regulated in energy-deprived Müller cells and glutamate uptake was significantly increased in the absence of glucose, as opposed to conditions with sodium depletion or in the presence of the EAAT-inhibitor tfb-TBOA, in which glutamate uptake was decreased. The intracellular glycogen content decreased in a time-dependent manner, whereas the ATP levels were sustained following energy deprivation. Co-cultures of RGC and Müller cells revealed better survival of glutamate treated RGC in the presence of Müller cells compared to controls. Energy deprivation of Müller cells enhanced their ability to protect RGC.
The present findings revealed an up-regulation of EAAT1 and EAAT2 in energy compromised Müller cells as well as an increased ability to remove glutamate from the extracellular space. Co-cultures of RGC and Müller cells revealed a protective role of Müller cells when RGC were exposed to glutamate. Hence, energy failure may result in an increased ability to protect RGC from glutamate-induced excitotoxicity, whereas malfunction of glutamate uptake in Müller cells may contribute to RGC death.
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