ИСТИНА

Iatrogenic corneal diseases can develop as a complication of ocular surgeries or interventions unrelated to visual system. Ultraviolet- induced corneal damage (UVCD) is a common consequence of photorefractive keratectomy, whereas perioperative dry eye syndrome (PDES) may be caused by prolonged general anesthesia. Importantly, these complications manifest as local inflammation, which being aggravated by infection or autoimmune/systemic factors, can give rise to keratitis or keratouveitis. The standard antiinflammatory treatment of the cornea involves corticosteroids possessing a number of side effects. Thus, there is a high demand for effective non-hormonal therapy specifically targeting inflammatory mechanisms in each corneal disease. Here, using rabbit models of UVCD and PDES, we demonstrate that the scenarios of ocular inflammation indeed significantly differ in these diseases. UVCD is characterized by a rapid inflammatory response, as loss of corneal epithelium and apoptosis of keratocytes are accompanied by stromal edema, neutrophil infiltration, and exudation of the anterior chamber of the eye. In PDES, inflammation has a slower and less pronounced course: a loss of epithelium is supplemented by inflammatory signs only on the late stages of the disease. Moreover, the differences between inflammatory mechanisms can be seen from distinct patterns of eicosanoids in the tear fluid. In UVCD, there is a pronounced increase in 12- HETE and decrease in 5-HETE indicating the activation of 12- lipoxygenase and 5-lipoxygenase pathways. In PDES, there are less prominent alterations in 12-HETE and 5-HETE, but an increase in 13-HOTrE pointing on involvement of 15-lipoxygenase. Our findings suggest that specific targeting the revealed inflammatory enzymes might be regarded as a prospective powerful therapy of the iatrogenic damage to the cornea induced by general anesthesia and UV-radiation. This study is supported by the Russian Science Foundation (Project no. 16-15-00255).