Abstract
Introduction
Ocular inflammation is a key pathogenic factor in most blindness-causing visual disorders. It can manifest in the aqueous humor (AH) and tear fluid (TF) as alterations in polyunsaturated fatty acids (PUFAs) and their metabolites, oxylipins, lipid mediators, which are biosynthesized via enzymatic pathways involving lipoxygenase, cyclooxygenase or cytochrome P450 monooxygenase and specifically regulate inflammation and resolution pathways.
Objectives
This study aimed to establish the baseline patterns of PUFAs and oxylipins in AH and TF by their comprehensive lipidomic identification and profiling in humans in the absence of ocular inflammation and comparatively analyze these compounds in the eye liquids of rabbits, the species often employed in investigative ophthalmology.
Methods
Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for qualitative and quantitative characterization of lipid compounds in the analyzed samples.
Results
A total of 28 lipid compounds were identified, including phospholipid derivatives and PUFAs, as well as 22 oxylipins. Whereas the PUFAs included arachidonic, docosahexaenoic and eicosapentaenoic acids, the oxylipins were derived mainly from arachidonic, linoleic and α-linolenic acids. Remarkably, although the concentration of oxylipins in AH was lower compared to TF, these liquids showed pronounced similarity in their lipid profiles, which additionally exhibited noticeable interspecies concordance.
Conclusion
The revealed correlations confirm the feasibility of rabbit models for investigating pathogenesis and trialing therapies of human eye disorders. The identified metabolite patterns suggest enzymatic mechanisms of oxylipin generation in AH and TF and might be used as a reference in ocular inflammation studies.
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Abbreviations
- AA:
-
Arachidonic acid
- AEA:
-
N-arachidonoylethanolamine
- AH:
-
Aqueous humor
- ALA:
-
α-Linolenic acid
- COX:
-
Cyclooxygenase
- CYP450:
-
Cytochrome P450 monooxygenase
- DES:
-
Dry eye syndrome
- DHA:
-
Docosahexaenoic acid
- DiHODE:
-
Dihydroxyoctadecadienoic acid
- DiHOME:
-
Dihydroxyoctadecamonoenoic acid
- EPA:
-
Eicosapentaenoic acid
- EpODE:
-
Epoxyoctadecadienoic acid
- EpOME:
-
Epoxyoctadecamonoenoic acid
- HDoHE:
-
Hydroxydocosahexaenoic acid
- HEPE:
-
Hydroxyeicosapentaenoic acid
- HETE:
-
Hydroxyeicosatetraenoic acid
- HODE:
-
Hydroxyoctadecadienoic acid
- HOTrE:
-
Hydroxyoctadecatrienoic acid
- HpODE:
-
Hydroperoxyoctadecadienoic acid
- HpOTrE:
-
Hydroperoxyoctadecatrienoic acid
- LA:
-
Linoleic acid
- LOX:
-
Lipoxygenase
- LT:
-
Leukotriene
- Lyso-PAF:
-
Lyso-platelet-activating factor
- OEA:
-
Oleoylethanolamide
- PG:
-
Prostaglandin
- PUFAs:
-
Polyunsaturated fatty acids
- TF:
-
Tear fluid
- UPLC-MS/MS:
-
Ultra-performance liquid chromatography-tandem mass spectrometry
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Acknowledgements
This study was supported by the Russian Science Foundation (Project No. 16-15-00255). The authors acknowledge the Preclinical Clinical Study Centre of RUDN University and “RUDN University Program 5-100” for their contribution to the development of the procedure of UPLC-MS/MS analysis.
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DVC, MGS, AAZ, PPP and EYZ conceived and designed research. VIK, EVF, OAK, AMB and ENI performed studies involving human participants. VVT, VEB and IIS conducted experiments with animals. DVC, NVA, AAA, SVG and VVC carried out mass-spectrometry analysis. SVG and VVC contributed new reagents or analytical tools. DVC, MGS, AAZ, PPP and EYZ analyzed data. DVC, NVA and EYZ visualized the results. EYZ wrote the manuscript. All authors read and approved the manuscript.
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Chistyakov, D.V., Azbukina, N.V., Astakhova, A.A. et al. Comparative lipidomic analysis of inflammatory mediators in the aqueous humor and tear fluid of humans and rabbits. Metabolomics 16, 27 (2020). https://doi.org/10.1007/s11306-020-1650-y
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DOI: https://doi.org/10.1007/s11306-020-1650-y