Tear Fluid Inflammatory Oxylipins in Perioperative Dry Eye Disease

Using the previously developed rabbit model of perioperative dry eye syndrome (PDES) and the method for quantitative mass spectrometric detection of oxylipins, it is shown that the development of corneal erosion under general anesthesia is associated with changes in tear fluid content of inflammatory metabolites including derivatives of linoleic (LA), alpha-linolenic (ALA), and arachidonic (AA) acids. The most significant growth is demonstrated for the metabolites of LA and ALA, while the content of AA derivatives (with the exception of 12-HETE) does not exhibit significant changes, indicating the key roles of the LA and ALA cascades in inflammatory response in PDES. An increase in oxylipins formed by nonenzymatic oxidation of LA (9-KODE) or its processing by cytochromes (12,13-EpOME) upon oxidative burst, indicates a significant contribution of oxidative stress to the PDES mechanism. The majority of metabolites of LA (13-HODE and 9-HODE), ALA (9-HOTrE and 13-HOTrE) and AK (12-HETE), the tear content of which is changed in PDES, are generated by the enzymes of the lipoxygenase family, while the concentration of cyclooxygenase products remains almost unchanged. 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 respect to PDES, which should be taken into account when developing complex therapy for this widespread socially significant disease.