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K. Gronert, R. J. Kemp, E. Walker, A. J. Leedom, A. Sullivan, B. Dong, A. Cohen, G. Zaidman; Distinct and Temporally Defined Changes in Lipid Mediator Profiles in Mouse Models of Corneal Injury and Neovascularization: Comparison to Human Corneas. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2383.
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Lipid autacoids are essential regulators of inflammation, wound healing and host defense. Recent reports have identified a central role for members of this large family of lipid autacoids, namely LXA4, 15-HETE, 12-HETrE, PGE2 and DHA-derived NPD1, in the inflammatory/reparative responses of the cornea. However, their identification and quantification is challenging and our understanding of lipid autacoid formation in the cornea is very limited. Hence, we employed LC/MS/MS-based lipidomic analyses to profile and quantify their formation in healthy and injured/inflamed human and mouse corneas.
Epithelial injury in anesthetized mice was generated by an Algerbrush and inflammatory neovascularization induced by placing a silk suture in the apex of the cornea. Corneas were collected prior to injury and 2, 7 or 14 days after injury. Discarded human corneal buttons from penetrating keratoplasty were collected within 60 min after surgery and immediately snap frozen. Lipid autacoids profiles were determined by mass spectrometry-based lipidomics employing a triple quadruple linear ion trap LC/MS/MS system and multiple reaction monitoring using established and specific transitions ions.
Lipidomic analyses demonstrated significant formation (0.1-100 pg) of established inflammatory and angiogenic lipid autacoids in human and mouse corneas. Epithelial injury and inflammatory neovascularization, each, exhibited distinct profiles with defined temporal changes that correlated with wound healing, inflammation and/or neovascularization. Lipidomic profiles in human corneas also demonstrated prominent formation of NPD1, 17-HDHA, PGE2, 15-HETE, 12-HETE, 12-HETrE and 5-HETE; each cornea exhibited a distinct lipidomic profile.
These results provide the first comprehensive profile of lipid autacoids in human and mouse corneas. Analyses demonstrate dynamic, temporally defined and distinct profiles of established pro- and anti-inflammatory and angiogenic lipid mediators in models of acute corneal injury. More importantly, these lipid mediators of inflammation and neovascularization were also identified as distinct profiles in human corneas. Collectively, these findings point towards a central role of lipid autacoids in the sequelae of corneal injury.
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