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Annamaria Maraschi, Folami Lamoke, Gregory I. Liou, Guido Ripandelli, Michele Mazzanti, Manuela Bartoli; The Chloride Intracellular Channel 1 (CLIC1) Modulates Amyloid Beta-induced Activation of Retinal Muller Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1818.
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© ARVO (1962-2015); The Authors (2016-present)
We have shown that retinal overexpression of amyloid beta (A-beta) results in neurodegeneration and activation of glial Muller cells, involving enhanced production of reactive oxygen species (ROS). Moreover, it has been shown that the chloride intracellular channel1 (CLIC1) mediates A-beta cytoxicity and ROS production in brain microglia cells. In this study we characterized the role of CLIC1 in mediating A-beta effects on Muller cells
Muller cells were stimulated with A-beta for different times (1, 2, 6 and 24 hours) at a concentration of 10 microM. Control cells were treated with vehicle only. Western analysis was used to assess the expression levels of CLIC1 at the different time points. Intracellular localization of CLIC1 protein was determined by immunocytochemical analysis. DCF assay was used to determinate ROS production in presence of A-beta and of CLIC1 specific inhibitor, IAA94 (100microM)
Western analysis showed that CLIC1 expression in Muller cells is increased in response to A-beta treatment. DCF staining revealed that A-beta treatment stimulates ROS production in Muller cells. This effect was significantly inhibited by blockade of CLIC1 activity with IAA94. In addition, A-beta stimulated CLIC1 perinuclear localization and colocalized it to the microtubular organization center (MTOC) which is involved in fagocytosis and disposal of misfolded proteins to aggresosomes
Our studies suggest that CLIC1 is a novel mediator of A-beta- induced activation of Muller cells, possibly by regulating the activation of stress response (i.e. ROS production and MTOC activation). Therefore, CLIC1is potentially involved in ocular diseases that have been implicated A-beta activity, such as glaucoma and age-related macular degeneration
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