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Sofia Pavlou, Josy Augustine, Sarah Doyle, Alan W Stitt, Matthew Campbell, Heping Xu, Mei Chen; Deletion of interleukin-33 (IL33) results in persistent Müller cell activation during retinal detachment. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5383. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
IL-33, a newly identified member of the IL-1 family, has diverse roles in immunity and inflammation. In the retina, IL-33 is exclusively expressed by Müller cells under physiological conditions. However, the role of IL-33 in Müller cell function and in retinal patho-physiology remains largely unknown. In this study, we investigated the role of IL-33 in Müller cell activation in a mouse model of retinal detachment (RD).
Retinal detachment was induced in adult wild-type (WT) C57BL/6J mice and IL-33-/- mice by subretinal injection of sodium hyaluronate (2μl/eye). At different times after induction of RD, eyes were collected and processed for immunohistochemistry. Müller cell activation was evaluated by upregulation of GFAP expression, while photoreceptor degeneration was assessed by immunostaining of cone arrestin and rhodopsin.
After retinal detachment for 24 hours, Müller cells became activated in both WT and IL-33-/- mice as evidenced by strong GFAP expression, which persisted for up to 7 days post-detachment. In WT mice subjected to retinal detachment, GFAP upregulation was accompanied by an increased intra-nuclear IL-33 expression in Müller cells. At 28 days post-detachment, GFAP expression was significantly reduced in WT mice when compared to IL-33-/- mice (p<0.05). In line with the higher GFAP expression in IL-33-/- mice, photoreceptor degeneration was also more severe in these retinas when compared to the WT mice at day 28 after retinal detachment.
The deletion of IL33 resulted in persistent Müller gliosis and more severe photoreceptor degeneration in our model of retinal detachment. Our results suggest that IL-33 negatively regulates Müller cell activation and protects photoreceptors from inflammation-mediated damage occurring as a consequence of retinal detachment.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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