Inflammatory Metabolites of Arachidonic Acid in Tear Fluid in UV-Induced Corneal Damage
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The ultraviolet (UV) B-induced damage of the eye surface of experimental animals (rabbits) includes total loss of corneal epithelium, apoptosis of keratocytes and stromal edema. These changes are accompanied by clinically and histologically manifested corneal inflammation, neutrophil infiltration, and exudation of the anterior chamber of the eye. According to results of mass spectrometric analysis, the UV-induced corneal damage is associated with pronounced changes in the tear lipid composition, including a decrease in the amount of arachidonic acid and prostaglandin E2 and an increase in the concentrations of prostaglandin D2 and its derivative 15d-PGJ2. In addition, it is accompanied by changes in the levels of hydroxyeicosate tetraenic acids, including a decrease of 12-HETE and an increase of 5-HETE. These changes suggest activation of metabolic pathways involving 5-lipoxygenase, 12-lipoxygenase, cyclooxygenases 1 and 2, and prostaglandin D synthase. These findings contribute to understanding mechanisms of UV-induced keratitis and point to feasibility of selective anti-inflammatory therapy for improving corneal regeneration after iatrogenic UV damage.
Keywords: UV-induced corneal damage keratocyte apoptosis keratitis tear film eicosanoids prostaglandin E2 prostaglandin D2 15d-PGJ2 5-HETE 12-HETE
This work was supported by the Russian Science Foundation, (project no. 16-15-00255; setting up a model of corneal UV damage in experimental animals (rabbits), clinical and histological analysis of normal and damaged cornea, collection and processing of tea samples from experimental animals, and identification of arachidonic acid metabolites present in it, analysis of the data obtained) and the PFUR program “5-100” (development of a mass spectrometric analysis method for arachidonic acid metabolites in rabbit tears).
COMPLIANCE WITH ETHICAL STANDARDS
All animal experiments were carried out in accordance with the recommendations of the 8th edition of the National Research Council, and also of the Statement for the Use of Animals in Ophthalmic and Visual Research of the Association for Research in Vision and Ophthalmology (ARVO). The protocol of this study was approved by the Committee on Bioethics of the Belozersky Institute of Physico-Chemical Biology (Moscow State University, protocol no. 1/2016).
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