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Satoshi Iwamoto, Tomoaki Koga, Min Liu, Akira Matsuda, Akira Murakami, Takehiko Yokomizo; 12-HHT accelerates corneal wound healing through leukotriene B4 receptor 2 (BLT2). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):713.
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© ARVO (1962-2015); The Authors (2016-present)
Leukotriene B4 receptor 2 (BLT2) is a high affinity receptor for 12-hydroxyheptadecatrienoic acid (12-HHT) whose production is inhibited by non-steroidal anti-inflammatory drugs (NSAIDs). We previously reported that BLT2 is expressed in small intestinal epithelial cells and skin keratinocytes, and plays important roles in intestinal barrier function and skin wound healing, respectively. Furthermore, some clinical papers reported that corneal epithelialization delays in patients treated with NSAIDs. Thus, we hypothesized that the delayed corneal wound healing in NSAIDs-treated patients is due to the inhibition of 12-HHT/BLT2 axis in the corneal epithelium. To test the hypothesis, corneal wound healing was compared between BLT2 WT and BLT2 KO mice.
Expression of BLT2 mRNA in the eye of Balb/c mouse was analyzed by real-time quantitative PCR. Eicosanoids in mouse whole eyes were quantified by LC-MS/MS. To make a corneal epithelial wound healing model, 2 mm diameter circle was made with trephine, and epithelial defect was created using a spatula (INAMI Inc.). Each corneal wound was photographed every 8 hours after the surgery until 72 hours. In case of diclofenac treatment model in WT mice, 1 % diclofenac eye drop started 2 days before the wound making (4 times/day).
BLT2 mRNA expression was observed in whole eye, especially in cornea and conjunctiva. We also confirmed that 12-HHT is present in murine eye. Furthermore, the corneal wound healing was delayed in BLT2 KO mice compared with BLT2 WT mice. Diclofenac treatment attenuated the production of 12-HHT in the eye, and significantly delayed corneal wound healing.
12-HHT/BLT2 axis promotes wound healing in cornea. Diclofenac treatment suppress the production of 12-HHT and inhibit the corneal wound healing.
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