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Mamoru Ogawa, Yosuke Isobe, tomoaki ishihara, Yuichi Uchino, Kazuo Tsubota, Makoto Arita; Role of eosinophil-derived lipid mediators in controlling corneal wound healing. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3226.
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Lipid mediators play important roles in regulating inflammatory responses and tissue homeostasis. For example, polyunsaturated fatty acid (PUFA)-derived lipid mediators such as lipoxinA4 and protectinD1,that are locally produced by 12/15-lipoxygenase (12/15-LOX), are reported to be protective against excessive inflammation and tissue damage.Also the protective role of 12/15-LOX-derived mediator circuit in the eye is previously reported (GronertK et al. J BiolChem280, 15267 (2005) ). In this study, we aim to determine comprehensive lipid mediator profiles in the course of corneal wound healing by LC-MS/MS-based mediator lipidomics. Also we aimed to identify the major cell types that express 12/15-LOX and potentially produce protective lipid mediators in the eye.
We established mouse corneal epithelium scratch model. We performed comprehensive analyses of PUFA metabolites by LC-MS/MS in the process of corneal wound healing. Next we investigated 12/15-LOX-expressing cells in the eye using flow cytometry and immunostaining.
In mouse corneal epithelium scratch model, 12/15-LOX knockout mice exhibited delayed wound healing. Comprehensive analyses of PUFA metabolites by LC-MS/MS revealed local production of a series of 12/15-LOX-derived mediators in the process of corneal wound healing. Next we determined 12/15-LOX-expressing cells in the eye. In CD45-positive cells, eosinophils were found to be the major cell type expressing 12/15-LOX. Eosinophil-deficient mice (ΔdblGATA) showed the delayed healing as compared to wild-type mice, and the production of 12/15-LOX-derived mediators were significantly reduced in ΔdblGATAmice.
We previously reported that 12/15-LOX-expressing eosinophils contribute to the resolution of acute peritonitis (Yamada T. et al. FASEB J 25,561 (2011)), and here we provide evidence that 12/15-LOX-expressing eosinophils may also play important roles in controlling corneal wound healing.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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