title: Identification and Profiling of Specialized Pro-Resolving Mediators in Human Tears by Lipid Mediator Metabolomics.
abstract: Specialized pro-resolving mediators (SPM), e.g. Resolvin D1, Protectin D1, Lipoxin A₄, and Resolvin E1 have each shown to be active in ocular models reducing inflammation. In general, SPMs have specific agonist functions that stimulate resolution of infection and inflammation in animal disease models. The presence and quantity of SPM in human emotional tears is of interest. Here, utilizing a targeted LC-MS-MS metabololipidomics based approach we document the identification of pro-inflammatory (Prostaglandins and Leukotriene B₄) and pro-resolving lipid mediators (D-series Resolvins, Protectin D1, and Lipoxin A₄) in human emotional tears from 12 healthy individuals. SPMs from the Maresin family (Maresin 1 and Maresin 2) were not present in these samples. Principal Component Analysis (PCA) revealed gender differences in the production of specific mediators within these tear samples as the SPMs were essentially absent in these female donors. These results indicate that specific SPM signatures are present in human emotional tears at concentrations known to be bioactive. Moreover, they will help to further appreciate the mechanisms of production and action of SPMs in the eye, as well as their physiologic roles in human ocular disease resolution.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Justin T
authors.initials: JT
authors.lastname: English
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Norris
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Hodges
authors.affiliation: Schepens Eye Research Institute/Massachusetts Eye and Ear, and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Dartt
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115. Electronic address: cserhan@bwh.harvard.edu.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D002853:Chromatography, Liquid; D004281:Docosahexaenoic Acids / Q000032:analysis*; D005260:Female; D006801:Humans; D017572:Leukotriene A4 / Q000032:analysis*; D044045:Lipoxins / Q000032:analysis*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D025341:Principal Component Analysis; D011453:Prostaglandins / Q000032:analysis*; D012727:Sex Characteristics; D053719:Tandem Mass Spectrometry; D013666:Tears / Q000737:chemistry*; D055815:Young Adult
chemical_list: D017572:Leukotriene A4; D044045:Lipoxins; D011453:Prostaglandins; C040527:lipoxin A4; C487679:protectin D1; C518399:resolvin D1; D004281:Docosahexaenoic Acids
keywords: Lipid Mediators; Omega-3 fatty acids; inflammation; protectins; resolution; resolvins