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Chenxi Yan, Xianqun Fan, Fushin X Yu; TARGETING INTERLEUKIN 1 SIGNALING PATHWAY AMELIORATES DIABETIC CORNEAL KERATOPATHY. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):745.
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To identify the role of Interleukin 1 receptor antagonist (IL1RN) in the suppression of IL-1 mediated inflammation and delayed wound healing in diabetic corneas and to evaluate the therapeutic potential of Anakinra (a rheumatoid arthritis drug, Kineret) to treat diabetic ocular complications.
The expression of IL1-β and IL1RN in homeostatic and healing corneal epithelial cells (CECs) of normal and Streptozotocin-induced type 1 diabetes C57BL/6 (B6) mice were assessed using PCR and immunohistochemistry. Immunohistochemistry of IL1RN was also performed using intact and organ cultured post-wounding normal and diabetic human corneas. The in vivo corneal epithelial wound healing rates were compared between diabetic corneas with or without Anakinra or normal corneas treated with or without Il1rn SiRNA. The expression levels of CXCL10 were assessed before and after treatment. In vivo corneal epithelial wound healing experiment was also performed in diabetic corneas with or without exogenous recombinant CXCL10 pretreatment.
The levels of IL-β and IL1RN were markedly elevated in normal CECs in response to wounding. In diabetic corneas, while the levels of IL1-β were increased, the expression of IL1RN was suppressed in healing CECs of both human and mouse corneas. Exogenous IL1RN accelerated delayed epithelial wound closure in the diabetic corneas while silencing IL1RN delayed epithelial wound closure in normoglycemia ones. PCR and Immunohistochemistry revealed a correlation between CXCL10 expression and the levels of IL1RN. Exogenous CXCL10 also alleviated the delay of epithelial wound healing in diabetic, but not normoglycemia corneas.
Suppressed expression of IL1RN in diabetic cornea may be an underlying mechanism for delayed diabetic wound healing which can alleviated by exogenous IL1RN. Anakinra, in addition to treating rheumatoid arthritis, may also be used as a preventative measure for reducing diabetic ocular complications.
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