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Mei Chen, Josy Augustine, Sofia Pavlou, Imran Ali, Sarah Doyle, Alan W Stitt, Matthew Campbell, Heping Xu; Interleukin-33 deficiency resulted in severe neuroretinal degeneration in retinal detachment. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3942.
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Müller cells are the principal glia in the retina and plays an essential role in maintaining retinal homeostasis and neuron cell functions. Interleukin 33 (IL-33), a member of the IL1 family, is exclusively expressed in the nuclei of Müller cells in the neural retina. IL-33 has diverse roles in immunity and inflammation although its role in Müller cell patho-physiology remains largely unknown. This study investigated the role of endogenous IL-33 to Müller glial function using a mouse model of retinal detachment (RD).
RD was induced in adult C57BL/6J (WT) and IL-33-/- mice by subretinal injection of sodium hyaluronate (2 μl/eye). Eyes were collected at different days after RD induction for immunohistochemistry (IHC) and RT-PCR. Scotopic ERG was performed at D28 post RD. Primary Müller cells from WT and IL-33-/- mice were cultured and exposed to normoxic or hypoxic conditions. Expression of neurotrophic factors were examined by RT-PCR. 661W Photoreceptors were treated with Müller cell conditioned medium and cell viability was examined using AlamarBlue viability assay.
Following RD, in WT mice, the expression of inflammatory cytokines including IL-1b, IL-6, CCL2, IL-33 was significant increased at Day 1; and then reduced gradually and returned to basal level by D28. IHC showed that IL-33 was exclusively located in the nuclei of Müller cells in both normal and RD retina. In IL-33-/- mice, RD induced acute inflammation; CCL2 and GFAP expression and immune cells infiltration was sustained for at least 28 days. The numbers of cone arrestin+ photoreceptors, GABAergic amacrine cells and ganglion cells were significantly lower in IL33-/- RD mice compared to WT RD mice. ERG revealed lower a- and b-wave amplitudes at D28 post-RD in IL-33-/- mice compared to WT RD mice. Primary Müller cells from IL-33-/- mice expressed significantly less neurotrophic factors including nerve growth factor, ciliary neurotrophic factor compared to WT Müller cells. IL-33-/- Müller cells failed to upregulate GS under hypoxia conditions.
IL-33-/- mice developed more severe retinal pathology following Retinal Detachment, and this is accompanied by sustained inflammation and reduced neurotrophic factor expression. Our data suggest that IL33 may have multiple roles in Müller cell function: (1) it may negatively control Müller cell activation, but (2) positively regulate neurotrophic factor expression.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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