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Sofia Pavlou, Richard Fitzgerald, Alan W Stitt, Mei Chen; Investigating the role of interleukin-33 (IL33) in Muller cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):406.
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© ARVO (1962-2015); The Authors (2016-present)
Muller cells are the major glial cell type in the retina. They provide structural, homeostatic and metabolic support to retinal neurons, release trophic and anti-oxidant molecules that are important for the maintenance and function of photoreceptors and regulate the formation and maintenance of the inner blood retinal barrier. Changes in Muller cell behaviour have been associated with a number of diseases, including diabetic retinopathy, macular telangiectasia type 2 and age-related macular degeneration. However, the mechanisms by which Muller cells mediate these diseases are elusive.<br /> IL-33, a newly identified cytokine, has been associated with several diseases, including atherosclerosis, experimental autoimmune uveitis and asthma. Interestingly, IL-33 is exclusively expressed by Muller cells within the retina. We therefore hypothesize that IL-33 may play an important role in regulating Muller cell function in inflammation related retinal diseases.
To determine the expression profile of IL33 and its receptor suppression of tumorigenicity 2 (ST2), murine eyes were cryosectioned and stained. The human Muller cell line MIO-M1 was stimulated with human recombinant IL33 at concentrations ranging from 10 ng/ml to 100 ng/ml. The expression levels of several genes were determined by qRT-PCR.
Within the retina, IL33 is exclusively expressed within the nuclei and ST2 within the processes of Muller cells. We used the MIO-M1 cell line in order to determine how activation of the IL33/ST2 pathway affects Muller cells. Exogenous IL33 leads to a reduction in the expression of chemokine (C-C motif) ligand 2 (CCL2), S100 calcium binding protein B (S100B) and IL10. In contrast, ST2, vascular endothelial growth factor A (VEGFA) and IL6 are increased in IL33-stimulated cells.
Exogenous IL33 can affect the behaviour of Muller cells in vitro, suggesting that abnormal activation of the IL33/ST2 pathway may be an underlying mechanism leading to the Muller cell-mediated defects in retinopathies.
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