34 research outputs found
Preventive Effects of Omega-3 and Omega-6 Fatty Acids on Peroxide Mediated Oxidative Stress Responses in Primary Human Trabecular Meshwork Cells
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
Common genetic determinants of intraocular pressure and primary open-angle Glaucoma
10.1371/journal.pgen.1002611PLoS Genetics85
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Macular Pigment Optical Density Measured by Heterochromatic Modulation Photometry
Purpose: To psychophysically determine macular pigment optical density (MPOD) employing the heterochromatic modulation photometry (HMP) paradigm by estimating 460 nm absorption at central and peripheral retinal locations. Methods: For the HMP measurements, two lights (B: 460 nm and R: 660 nm) were presented in a test field and were modulated in counterphase at medium or high frequencies. The contrasts of the two lights were varied in tandem to determine flicker detection thresholds. Detection thresholds were measured for different R:B modulation ratios. The modulation ratio with minimal sensitivity (maximal threshold) is the point of equiluminance. Measurements were performed in 25 normal subjects (11 male, 14 female; age: 30±11 years, mean ± sd) using an eight channel LED stimulator with Maxwellian view optics. The results were compared with those from two published techniques – one based on heterochromatic flicker photometry (Macular Densitometer) and the other on fundus reflectometry (MPR). Results: We were able to estimate MPOD with HMP using a modified theoretical model that was fitted to the HMP data. The resultant MPODHMP values correlated significantly with the MPODMPR values and with the MPODHFP values obtained at 0.25° and 0.5° retinal eccentricity. Conclusions: HMP is a flicker-based method with measurements taken at a constant mean chromaticity and luminance. The data can be well fit by a model that allows all data points to contribute to the photometric equality estimate. Therefore, we think that HMP may be a useful method for MPOD measurements, in basic and clinical vision experiments.</sub
Hsp27 and Hsp90 expression analysis.
<p>(<b>A</b>) Quantification of realtime PCR expression analysis of Hsp27 and Hsp90 mRNAs in controls, ω-6 and ω-3 fatty acids pre-treated hTM normalized to controls. (<b>B</b>) Western blot detection of cellular Hsp27, Hsp90 and actin protein in controls, ω-6 and ω-3 fatty acids pre-treated hTM. (<b>C</b>) Plot of densitometric quantifications of Hsp27 and Hsp90 protein expression in controls, ω-6 and ω-3 fatty acids pre-treated hTM adjusted to actin expression and normalized to controls. Values represent m.a. ± sd of three independent experiments performed on cells of three different donors (n = 9); asterisks: p-values of statistical significances (*p≤0.05; **p≤0.01; ***p≤0.001).</p