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. 2020 May;98(5):751-760.
doi: 10.1007/s00109-020-01907-w. Epub 2020 Apr 20.

Signaling lipids as diagnostic biomarkers for ocular surface cicatrizing conjunctivitis

Antonio Di Zazzo  1 , Wei Yang  2 , Marco Coassin  1 , Alessandra Micera  3 , Marco Antonini  1 , Fabrizio Piccinni  1 , Maria De Piano  4 , Isabelle Kohler  5 , Amy C Harms  2 , Thomas Hankemeier  2 , Stefano Boinini  1 , Alireza Mashaghi  6
Affiliations

Signaling lipids as diagnostic biomarkers for ocular surface cicatrizing conjunctivitis

Antonio Di Zazzo et al. J Mol Med (Berl). 2020 May.

Erratum in

Abstract

Metabolomics has been applied to diagnose diseases, predict disease progression, and design therapeutic strategies in various areas of medicine. However, it remains to be applied to the ocular surface diseases, where biological samples are often of limited quantities. We successfully performed proof-of-concept metabolomics assessment of volume-limited cytology samples from a clinical form of chronic inflammatory cicatrizing conjunctivitis, i.e., ocular MMP and discovered metabolic changes of signaling lipid mediators upon disease onset and progression. The metabolomics assessment revealed active oxylipins, lysophospholipids, fatty acids, and endocannabinoids alterations, from which potential biomarkers linked to inflammatory processes were identified. Possible underlying mechanisms such as dysregulated enzyme activities (e.g., lipoxygenases, cytochrome P450, and phospholipases) were suggested which may be considered as potential therapeutic targets in future studies. KEY MESSAGES: Metabolic profile of the ocular surface can be measured using impression cytology samples. Metabolomics analysis of ocular pemphigoid is presented for the first time. The metabolomics assessment of OCP patients revealed active oxylipins, lysophospholipids, fatty acids, and endocannabinoids alterations. Several oxylipins are identified as diagnostic biomarkers for OCP.

Keywords: Cicatrizing conjunctivitis; LC-MS/MS; Metabolomics; Mucous membrane pemphigoid; Signaling lipid mediators.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Confocal analysis of ocular cicatricial pemphigoid diagnosis by polyvalent IgG. Direct immune fluorescence IgG/propidium iodide, merge, × 20
Fig. 2
Fig. 2
Signaling lipid mediators (oxylipins) in control group and ocular MMP patients. a Oxylipins-LOX pathway. b Oxylipins-CYP450 pathway. c Oxylipins-ROS pathway. The intensity represents the relative quantitation of each metabolite
Fig. 3
Fig. 3
Signaling lipid mediators (lysophospholipids and fatty acids) in control group and ocular MMP patients. a Lysophosphatidic acids (LPAs) and cyclic-lysophosphatidic acids (cLPAs). b Lysophosphatidylethanolamines (LPEs). c Lysophosphatidylglycerols (LPGs). d Lysophosphatidylinositol (LPIs). e Lysophosphatidylserines (LPSs). f Fatty acids. The intensity represents the relative quantitation of each metabolite
Fig. 4
Fig. 4
Signaling lipid mediators (endocannabinoids) in control group and ocular MMP patients. The intensity represents the relative quantitation of each metabolite
Fig. 5
Fig. 5
Signaling lipid mediators as potential biomarker candidates for ocular MMP diagnosis: 9(S)-HOTrE and (±)5-HEPE. Data is shown in absolute concentration (nM) of the metabolite in conjunctival biopsies in controls and ocular MMP patients, respectively, calculated based on the calibration curve which is shown in the insert figure
Fig. 6
Fig. 6
Signaling lipid mediators as mid-late-staging indicators. A panel of oxylipins (a) and lysophospholipids (b–f) significantly increased from stage II to stage III. The intensity represents the relative quantitation of each metabolite
See this image and copyright information in PMC

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