Researchers in Section of Pharmacotherapy – University of Copenhagen

Oxidative Stress-Induced Dysfunction of Muller Cells During Starvation

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Anne Katrine Toft-Kehler, Iswariyaraja Sridevi Gurubaran, Claus Desler Madsen, Lene J. Rasmussen, Dorte Marie Skytt, Miriam Kolko

PURPOSE. Muller cells support retinal neurons with essential functions. Here, we aim to examine the impact of starvation and oxidative stress on glutamate uptake and mitochondrial function in Muller cells.

METHODS. Cultured human retinal Muller cells (MIO-M1) were exposed to H2O2 and additional starvation for 24 hours. Effects of starvation and H2O2 on glutamate uptake and mitochondrial function were assessed by kinetic glutamate uptake assays and Seahorse assays, respectively. Cell survival was evaluated by cell viability assays. mRNA and protein expressions were assessed by quantitative PCR and Western blot.

RESULTS. Starvation of Muller cells increased the glutamate uptake capacity as well as the expression of the most abundant glutamate transporter, EAAT1. Mitochondrial and glycolytic activity were diminished in starved Muller cells despite unaffected cell viability. Simultaneous starvation and exposure to oxidative stress resulted in a reduced glutamate uptake and a collapsed mitochondrial function. In Muller cells with intact energy supply, the glutamate uptake and mitochondrial function were unaffected after exposure to oxidative stress.

CONCLUSIONS. Here, we identify an increased susceptibility toward oxidative stress in starved Muller cells in spite of unaffected viability and an apparent decreased ability to transport glutamate. Solely exposure to oxidative stress did not affect Muller cell functions. Thus, our study suggests an increased susceptibility of Muller cells in case of more than one cellular stressor. Extrapolating these findings, age-related neurodegenerative retinal diseases may be the result of impaired Muller cell function.
Original languageEnglish
JournalInvestigative Ophthalmology & Visual Science
Volume57
Issue number6
Pages (from-to)2721-2728
ISSN0146-0404
DOIs
Publication statusPublished - May 2016

    Research areas

  • Muller cells, starvation, oxidative stress, glutamate uptake, mitochondrial function

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