TY - JOUR
T1 - Retinal vasculopathy is reduced by dietary salt restriction: involvement of Glia, ENaCa, and the renin-angiotensin-aldosterone system
AU - Deliyanti, Devy
AU - Armani, Roksana
AU - Casley, David John
AU - Figgett, William Arthur
AU - Agrotis, Alexander
AU - Wilkinson-Berka, Jennifer
PY - 2014
Y1 - 2014
N2 - 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
AB - 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
UR - http://atvb.ahajournals.org/content/34/9/2033.full.pdf+html
U2 - 10.1161/ATVBAHA.114.303792
DO - 10.1161/ATVBAHA.114.303792
M3 - Article
SN - 1079-5642
VL - 34
SP - 2033
EP - 2041
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 9
ER -