ИСТИНА

Glaucoma is a severe ocular disease associated with abnormalities in aqueous humor (AH) circulation and an increase in intraocular pressure (IOP) leading to damage to retinal ganglion cells, progressive optical neuropathy, and loss of vision. The common idiopathic form of the disease is primary open-angle glaucoma (POAG) characterized by complex pathophysiological mechanisms involving oxidative stress, excitotoxicity, and other factors, which can contribute to IOP increase and ganglion cell death. In this study, we report novel insights into the pathogenesis of POAG gained from targeted lipidomic studies focusing on lipid mediators – omega-3 and omega-6 polyunsaturated fatty acids, and their derivatives oxylipins. Previous studies indicated that some of these compounds (prostaglandins) regulate AH outflow, and therefore can be employed for the treatment of glaucoma. Using biological samples collected from a cohort of POAG patients and healthy individuals, we examined alterations in the content of polyunsaturated fatty acids and oxylipins in AH accompanying IOP growth, and progression of the disease. A total of 19 signaling lipids were identified, including three polyunsaturated fatty acids, fourteen oxylipins, and two phospholipid derivatives. Despite the variety of the identified mediators, the POAG-related alterations were provided by a small set of these compounds, the pattern of which pointed to oxidative stress as a critical pathological factor in POAG. Interestingly, similar lipidomic alterations were found in tear fluid of the same patients indicating a diagnostic value of its content in glaucoma, especially since this eye liquid can be collected using a non-invasive procedure. This study was supported by the Russian Science Foundation (Project no. 21-15-00123).