linoleic-acid and Macular-Degeneration

Although the role of n-6 polyunsaturated fatty acids (PUFAs) in age-related macular degeneration (AMD) has been studied in previous observational studies, the precise manner in which 1 or more n-6 PUFAs account for this relationship remains unclear.. Using genetic instruments for n-6 PUFAs traits implemented through mendelian randomization (MR), we aimed to study possible causal associations between n-6 PUFAs and AMD.. The 2-sample MR method was used to obtain unconfounded causal estimates. We selected genetic variants strongly associated (P < 5 × 10-8) with circulating linoleic acid (LA) and arachidonic acid (AA) from a study involving 8 631 individuals and applied to an AMD case-control study (33 526 participants and 16 144 cases). The weighted median and MR Egger methods were used for the sensitivity analysis.. Our MR analysis suggested that circulating LA was a causal protective factor for AMD, with an odds ratio (OR) estimate of 0.967 (95% CI 0.945 to 0.990; P = .005) per percentage in total fatty acid increase in LA. In contrast, higher genetically predicted circulating AA causally increased the AMD risk (OR = 1.034; 95% CI 1.012 to 1.056; P = .002). Sensitivity analysis provided no indication of unknown pleiotropy. The findings from different single-nucleotide polymorphism selections and analytic methods were consistent, suggesting the robustness of the causal associations.. Our study provided genetic evidence that circulating LA accounted for protective effects of n-6 PUFAs against the risk of AMD, whereas AA was responsible for deleterious effects on higher AMD risk.

Topics: Aged; Aged, 80 and over; Aging; Arachidonic Acid; Case-Control Studies; Causality; Fatty Acids, Omega-6; Female; Genome-Wide Association Study; Humans; Linoleic Acid; Macular Degeneration; Male; Mendelian Randomization Analysis; Middle Aged; Polymorphism, Single Nucleotide; Protective Factors; Risk Factors

To investigate whether docosahexaenoic acid (DHA) could inhibit linoleic acid (LA) induced monocyte chemoattractant protein (MCP)-1 expression in human retinal pigment epithelial (RPE) cells.. ARPE-19 cells were pretreated with DHA and then exposed to LA. The expression of MCP-1 and PPARγ was examined using RT-PCR and Western blot analysis. LA at 10, 25, or 50 μM induced expression of MCP ARPE-19 cells in a dose-dependent manner (p < 0.05). DHA at 50 and 100 μM effectively inhibited LA-induced MCP-1 expression and production (p < 0.05) and NF-κB activation. In addition, the culture medium from LA-stimulated ARPE-19 cells could induce tube formation in choroidal endothelial cells (RF6A), whereas 100 μM DHA inhibited tube formation. DHA at 100 μM increased the expression and activity of PPARγ (p < 0.05). Pretreatment with PPARγ inhibitor (GW9662) abolished the inhibitory effect of DHA (100 μM) on LA-induced IκB degradation, p65 translocation, and MCP-1 expression in ARPE-19 cells (p < 0.05), as well as tube formation in RF6A.. DHA reduced LA-induced MCP-1 expression via a PPARγ- and NF-κB-dependent pathway in ARPE-19 cells. These results suggest the molecular mechanisms underlying the beneficial effects of increased consumption of DHA and reduced consumption of LA on age-related macular degeneration.

Topics: Anilides; Arachidonic Acid; Cell Line; Chemokine CCL2; Choroid; Choroidal Neovascularization; Culture Media, Conditioned; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Nonesterified; Humans; Linoleic Acid; Macular Degeneration; NF-kappa B; Osmolar Concentration; PPAR gamma; Promoter Regions, Genetic; Retinal Pigment Epithelium; Signal Transduction; Up-Regulation

Evidence continues to accumulate that oxidative stress is etiologically important in the pathogenesis of age-related maculopathy (ARM) and that appropriate antioxidants of dietary origin may protect against this condition.. Risk factors for ARM may be classed as established or putative. We report a study designed to investigate whether such risk factors are associated with a dietary lack of antioxidants relevant to retinal health.. Dietary, anthropometric, and sociodemographic details relating to 828 healthy Irish subjects aged 20-60 y were recorded in a cross-sectional fashion and analyzed for associations between risk factors for ARM and dietary intake of relevant nutrients.. Of the established risk factors for ARM, increasing age was associated with a relative lack of dietary zeaxanthin (P < 0.05) and tobacco use with a relative lack of dietary vitamin C (P < 0.05). Of the putative risk factors for ARM, alcohol consumption was associated with a relative lack of dietary alpha-linoleic acid (P < 0.05), and female sex was associated with a relative lack of dietary zinc (P < 0.05).. We showed that several variables related to risk for ARM are associated with a relative dietary lack of key nutrients. Our finding that age, the most important and universal risk factor for ARM, is associated with a relative lack of dietary zeaxanthin, is an important finding that warrants further investigation.

Topics: Adult; Age Factors; Alcohol Drinking; Antioxidants; Ascorbic Acid; Cross-Sectional Studies; Diet; Female; Humans; Ireland; Linoleic Acid; Macular Degeneration; Male; Middle Aged; Oxidative Stress; Risk Factors; Sex Factors; Smoking; Surveys and Questionnaires; Xanthophylls; Zeaxanthins; Zinc

Topics: Aged; beta Carotene; Diet; Female; Follow-Up Studies; Humans; Linoleic Acid; Lutein; Macular Degeneration; Male; Middle Aged; Xanthophylls; Zeaxanthins

Topics: Cohort Studies; Diet; Humans; Linoleic Acid; Lutein; Macular Degeneration; Middle Aged; Photography; Xanthophylls; Zeaxanthins

To evaluate the relationship between intake of total and specific types of fat and risk for advanced age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults.. A multicenter eye disease case-control study.. Five US clinical ophthalmology centers.. Case subjects included 349 individuals (age range, 55-80 years) with the advanced, neovascular stage of AMD diagnosed within 1 year of their enrollment into the study who resided near a participating clinical center. Control subjects included 504 individuals without AMD but with other ocular diseases. Controls were from the same geographic areas as cases and were frequency-matched to cases by age and sex.. Relative risk for AMD according to level of fat intake, controlling for cigarette smoking and other risk factors.. Higher vegetable fat consumption was associated with an elevated risk for AMD. After adjusting for age, sex, education, cigarette smoking, and other risk factors, the odds ratio (OR) was 2.22 (95% confidence interval [CI], 1.32-3.74) for persons in the highest vs those in the lowest quintiles of intake (P for trend,.007). The risk for AMD was also significantly elevated for the highest vs lowest quintiles of intake of monounsaturated (OR, 1.71) and polyunsaturated (OR, 1.86) fats (Ps for trend,.03 and.03, respectively). Higher consumption of linoleic acid was also associated with a higher risk for AMD (P for trend,.02). Higher intake of omega-3 fatty acids was associated with a lower risk for AMD among individuals consuming diets low in linoleic acid, an omega-6 fatty acid (P for trend,.05; P for continuous variable,.03). Similarly, higher frequency of fish intake tended to reduce risk for AMD when the diet was low in linoleic acid (P for trend,.05). Conversely, neither omega-3 fatty acids nor fish intake were related to risk for AMD among people with high levels of linoleic acid intake.. Higher intake of specific types of fat--including vegetable, monounsaturated, and polyunsaturated fats and linoleic acid--rather than total fat intake may be associated with a greater risk for advanced AMD. Diets high in omega-3 fatty acids and fish were inversely associated with risk for AMD when intake of linoleic acid was low.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Diet Records; Dietary Fats; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Feeding Behavior; Female; Humans; Linoleic Acid; Macular Degeneration; Male; Middle Aged; Odds Ratio; Risk Factors; United States