Abstract
Simple SummaryAnalysis of the eye liquids collected from a cohort of primary open-angle glaucoma patients identified signaling lipids, the pattern of which suggests a role of arachidonic acid/platelet activating-factor (PAF)-dependent pathways and oxidative stress in the pathogenesis of the disease and provides novel targets for its diagnostics and treatment.Primary open-angle glaucoma (POAG) is characterized by degeneration of retinal ganglion cells associated with an increase in intraocular pressure (IOP) due to hindered aqueous humor (AH) drainage through the trabecular meshwork and uveoscleral pathway. Polyunsaturated fatty acids and oxylipins are signaling lipids regulating neuroinflammation, neuronal survival and AH outflow. Among them, prostaglandins have been previously implicated in glaucoma and employed for its treatment. This study addressed the role of signaling lipids in glaucoma by determining their changes in AH accompanying IOP growth and progression of the disease. Eye liquids were collected from patients with POAG of different stages and cataract patients without glaucoma. Lipids were identified and quantified by UPLC-MS/MS. The compounds discriminating glaucoma groups were recognized using ANCOVA and PLS-DA statistic approaches and their biosynthetic pathways were predicted by bioinformatics. Among 22 signaling lipids identified in AH, stage/IOP-dependent alterations in glaucoma were provided by a small set of mediators, including 12,13-DiHOME, 9- and 13-HODE/KODE, arachidonic acid and lyso-PAF. These observations correlated with the expression of cytochromes P450 (CYPs) and phospholipases A2 in the ocular tissues. Interestingly, tear fluid exhibited similar lipidomic alterations in POAG. Overall, POAG may involve arachidonic acid/PAF-dependent pathways and oxidative stress as evidenced from an increase in its markers, KODEs and 12,13-DiHOME. The latter is a product of CYPs, one of which, CYP1B1, is known as POAG and primary congenital glaucoma-associated gene. These data provide novel targets for glaucoma treatment. Oxylipin content of tear fluid may have diagnostic value in POAG.
Highlights
Glaucoma is a highly prevalent neurodegenerative ocular disorder affecting more than 70 million people worldwide
Using targeted lipidomic analysis, we have demonstrated that the main types of signaling lipids, such as polyunsaturated fatty acids (PUFAs), oxylipins and phospholipid derivatives, are secreted in normal aqueous humor (AH) and their patterns are significantly altered in various ocular disorders, including those affecting the retina [24,25,26]
The study involved a total of 24 patients with Primary open-angle glaucoma (POAG) and 14 cataract patients without a history of glaucoma that were used as controls
Summary
Glaucoma is a highly prevalent neurodegenerative ocular disorder affecting more than 70 million people worldwide In most cases, it is characterized by a transient or sustained increase in intraocular pressure (IOP) leading to apoptotic death of retinal ganglion cells (RGCs), loss of the retinal nerve fiber layer and excavation of the optic nerve head. Development of primary open-angle glaucoma (POAG) is related to a malfunctioning of the TM and/or aberrations of the structural and biomechanical features of the corneoscleral membrane. It is affected by metabolic, genetic and environmental conditions, as well as myopia and aging [1,3,4]. Recent findings highlighted the pathogenic role of low-grade inflammation driven by some of these factors
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