Retinal vasculopathy is reduced by dietary salt restriction: involvement of Glia, ENaCα, and the renin-angiotensin-aldosterone system.

OBJECTIVE: Neovascularization and vaso-obliteration are vision-threatening events that develop by interactions between retinal vascular and glial cells. A high-salt diet is causal in cardiovascular and renal disease, which is linked to modulation of the renin-angiotensin-aldosterone system. However, it is not known whether dietary salt influences retinal vasculopathy and if the renin-angiotensin-aldosterone system is involved. We examined whether a low-salt (LS) diet influenced vascular and glial cell injury and the renin-angiotensin-aldosterone system in ischemic retinopathy. APPROACH AND RESULTS: Pregnant Sprague Dawley rats were fed LS (0.03% NaCl) or normal salt (0.3% NaCl) diets, and ischemic retinopathy was induced in the offspring. An LS diet reduced retinal neovascularization and vaso-obliteration, the mRNA and protein levels of the angiogenic factors, vascular endothelial growth factor, and erythropoietin. Microglia, which influence vascular remodeling in ischemic retinopathy, were reduced by LS as was tumor necrosis factor-α. Macroglial Müller cells maintain the integrity of the blood-retinal barrier, and in ischemic retinopathy, LS reduced their gliosis and also vascular leakage. In retina, LS reduced mineralocorticoid receptor, angiotensin type 1 receptor, and renin mRNA levels, whereas, as expected, plasma levels of aldosterone and renin were increased. The aldosterone/mineralocorticoid receptor-sensitive epithelial sodium channel alpha (ENaCα), which is expressed in Müller cells, was increased in ischemic retinopathy and reduced by LS. In cultured Müller cells, high salt increased ENaCα, which was prevented by mineralocorticoid receptor and angiotensin type 1 receptor blockade. Conversely, LS reduced ENaCα, angiotensin type 1 receptor, and mineralocorticoid receptor expression. CONCLUSIONS: An LS diet reduced retinal vasculopathy, by modulating glial cell function and the retinal renin-angiotensin-aldosterone system.

Circulating omega-3 Fatty acids and neovascular age-related macular degeneration.

PURPOSE: We assessed the associations of serum, red blood cell membranes (RBCM) and dietary long-chain n-3 polyunsaturated fatty acids (LC-PUFAs) with neovascular age-related macular degeneration (AMD). METHODS: We included 290 patients of the Nutritional AMD Treatment 2 Study (NAT2) with neovascular AMD in one eye and early AMD lesions in the other eye, and 144 normal vision controls without AMD. Dietary intake of seafood was estimated by food frequency questionnaire. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) composition in serum and RBCM were determined by gas chromatography from 12-hour fasting blood samples and was expressed as percentages of total fatty acids profile. Logistic regressions estimated associations of neovascular AMD with dietary intake of seafood and circulating n-3 LC-PUFAs. RESULTS: Dietary oily fish and seafood intake were significantly lower in AMD patients than in controls. After adjustment for all potential confounders (age, sex, CFH Y402H, ARMS2 A69S, and ApoE4 polymorphisms, plasma triglycerides, hypertension, hypercholesterolemia, and family history of AMD), serum EPA was associated significantly with a lower risk for neovascular AMD (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.22-0.77; P = 0.005). Analysis of RBCM revealed that EPA and EPA+DHA were associated significantly with a lower risk for neovascular AMD (OR = 0.25; 95% CI, 0.13-0.47; P < 0.0001 and OR = 0.52; 95% CI, 0.29-0.94; P = 0.03, respectively). CONCLUSIONS: The RBCM EPA and EPA+DHA, as long-term biomarkers of n-3 dietary PUFA status, were associated strongly with neovascular AMD and may represent an objective marker identifying subjects at high risk for neovascular AMD, who may most benefit from nutritional interventions. (http://www.controlled-trials.com/isrctn number, ISRCTN98246501).