Abstract
Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H2O2, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H2O2 further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H2O2 stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H2O2 mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H2O2 induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be the more beneficial fatty acid in respect of prophylactic intake for prevention of a glaucomatous disease.
Highlights
The trabecular meshwork (TM) accounts for about 70–90% of total aqueous humor (AH) outflow from the anterior chamber in the adult human eye
Effects of v-6 (16 mM) and v-3 (50 mM) fatty acids compared to controls (Co). (B) Effects of H2O2 in controls, v-6 and v-3 fatty acids pre-treated human TM cells (hTM). (C) %-reduction of BrdU-incorporation after H2O2 exposition
Prophylactic intake of dietary supplements with alleged antioxidant capacities is recommended for protection from deleterious effects of oxidative stress and prevention of glaucoma thereby
Summary
The trabecular meshwork (TM) accounts for about 70–90% of total aqueous humor (AH) outflow from the anterior chamber in the adult human eye. The TM constitutes an outflow resistance and thereby determines the intraocular pressure (IOP). Increase of outflow resistance and IOP, eventually, is a major risk factor in primary open angle glaucoma (POAG) [1]. POAG patients exhibit specific morphological peculiarities as accumulations of extracellular matrix material (ECM) and condensation or clustering of the cytoskeleton. Deregulations on the cellular level affecting signaling pathways regulating apoptosis, cellular senescence and cell cycle control were observed in ocular cells of POAG patients [1,2,3,4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
