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

Devy Deliyanti, Roksana Armani, David John Casley, William Arthur Figgett, Alexander Agrotis, Jennifer Wilkinson-Berka

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16 Citations (Scopus)


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-a. Macroglial Muller 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 (ENaCa), which is expressed in Muller cells, was increased in ischemic retinopathy and reduced by LS. In cultured Muller cells, high salt increased ENaCa, which was prevented by mineralocorticoid receptor and angiotensin type 1 receptor blockade. Conversely, LS reduced ENaCa, 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
Original languageEnglish
Pages (from-to)2033 - 2041
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number9
Publication statusPublished - 2014

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