Oxidative Stress-Induced Dysfunction of Muller Cells During Starvation
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Oxidative Stress-Induced Dysfunction of Muller Cells During Starvation. / Toft-Kehler, Anne Katrine; Gurubaran, Iswariyaraja Sridevi; Madsen, Claus Desler; Rasmussen, Lene J.; Skytt, Dorte Marie; Kolko, Miriam.
I: Investigative Ophthalmology & Visual Science, Bind 57, Nr. 6, 05.2016, s. 2721-2728.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Oxidative Stress-Induced Dysfunction of Muller Cells During Starvation
AU - Toft-Kehler, Anne Katrine
AU - Gurubaran, Iswariyaraja Sridevi
AU - Madsen, Claus Desler
AU - Rasmussen, Lene J.
AU - Skytt, Dorte Marie
AU - Kolko, Miriam
PY - 2016/5
Y1 - 2016/5
N2 - 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.
AB - 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.
KW - Muller cells
KW - starvation
KW - oxidative stress
KW - glutamate uptake
KW - mitochondrial function
U2 - 10.1167/iovs.16-19275
DO - 10.1167/iovs.16-19275
M3 - Journal article
C2 - 27196320
VL - 57
SP - 2721
EP - 2728
JO - Investigative Ophthalmology & Visual Science
JF - Investigative Ophthalmology & Visual Science
SN - 0146-0404
IS - 6
ER -
ID: 166664125