Using the previously developed rabbit model of perioperative dry eye syndrome (PDES) and quantitative mass spectrometric technique it is shown that the development of corneal erosion under conditions of general anesthesia is associated with changes in the content of inflammatory metabolites, namely, derivatives of linoleic (LA), alpha-linolenic (ALA), and arachidonic (AA) acids in tear fluid. The increase in the content of the metabolites of LA and ALA is found to be the most significant, while the content of AA derivatives (with the exception of 12-HETE) remains almost unchanged, indicating the key roles of the LA and ALA cascades in the inflammatory response in PDES. The increase in the concentration of oxylipins that can be formed by nonenzymatic oxidation of LA (9-KODE) or its processing by cytochromes (12,13-EpOME) under oxidative conditions indicates a significant contribution of oxidative stress to the development of PDES. The majority of metabolites of LA (13-HODE and 9-HODE), ALA (9-HOTrE and 13-HOTrE) and AA (12-HETE), the tear content of which was changed in PDES, are generated by the enzymes of lipoxygenase family. By contrast, the concentration of cyclooxygenase products does not exhibit any significant fluctuations. These data suggest a low therapeutic potential of cyclooxygenase inhibitors (such as nonsteroidal anti-inflammatory drugs) and a high therapeutic potential of antioxidants and lipoxygenase inhibitors in PDES, which should be taken into account upon developing a complex therapy for this disease.
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The work was supported by the Russian Science Foundation (project no. 16-15-00255). The mass-spectroscopic method of the detection of metabolites in the rabbit tear was developed with the support of the Program 5-100 of the Peoples’ Friendship University of Russia.
The authors state that they have no conflict of interest.
Experiments were conducted in accordance with the recommendations of the 8th edition of the Guide for the Care and Use of Laboratory Animals of the National Research Council and Statement for the Use of Animals in Ophthalmic and Visual Research of the Association for Research in Vision and Ophthalmology (ARVO). Experimental protocols were approved by the Bioethics committee of the Belozersky Research Institute of Physical and Chemical Biology of the Moscow Lomonosov State University.
Translated by E. Puchkov
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Chistyakov, D.V., Azbukina, N.V., Astakhova, A.A. et al. Alterations in Tear Content of Inflammatory Oxylipines Associated with Perioperative Dry Eye Syndrome. Biochem. Moscow Suppl. Ser. A 14, 134–139 (2020). https://doi.org/10.1134/S1990747819060047
- corneal erosion
- general anesthesia
- dry eye syndrome
- tear fluid
- oxidative stress