title: Retinal vasculopathy is reduced by dietary salt restriction: involvement of Glia, ENaCα, and the renin-angiotensin-aldosterone system.
abstract: 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.
  
  
  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.
authors.affiliation: From the Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia (D.D., R.A., W.A.F., A.A., J.L.W.-B.); and Prosearch International, Malvern, Victoria, Australia (D.C.).
authors.forename: Devy
authors.initials: D
authors.lastname: Deliyanti
authors.affiliation: From the Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia (D.D., R.A., W.A.F., A.A., J.L.W.-B.); and Prosearch International, Malvern, Victoria, Australia (D.C.).
authors.forename: Roksana
authors.initials: R
authors.lastname: Armani
authors.affiliation: From the Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia (D.D., R.A., W.A.F., A.A., J.L.W.-B.); and Prosearch International, Malvern, Victoria, Australia (D.C.).
authors.forename: David
authors.initials: D
authors.lastname: Casely
authors.affiliation: From the Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia (D.D., R.A., W.A.F., A.A., J.L.W.-B.); and Prosearch International, Malvern, Victoria, Australia (D.C.).
authors.forename: William A
authors.initials: WA
authors.lastname: Figgett
authors.affiliation: From the Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia (D.D., R.A., W.A.F., A.A., J.L.W.-B.); and Prosearch International, Malvern, Victoria, Australia (D.C.).
authors.forename: Alex
authors.initials: A
authors.lastname: Agrotis
authors.affiliation: From the Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia (D.D., R.A., W.A.F., A.A., J.L.W.-B.); and Prosearch International, Malvern, Victoria, Australia (D.C.). jennifer.wilkinson-berka@monash.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wilkinson-Berka
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000032:analysis; D000450:Aldosterone / Q000097:blood / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D051401:Aquaporin 4 / Q000096:biosynthesis / Q000235:genetics; D001835:Body Weight; D002478:Cells, Cultured; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D004327:Drinking Behavior; D063928:Ependymoglial Cells / Q000737:chemistry / Q000473:pathology; D053503:Epithelial Sodium Channels / Q000502:physiology*; D004921:Erythropoietin / Q000032:analysis; D005911:Gliosis / Q000209:etiology / Q000503:physiopathology; D006400:Hematocrit; D017136:Ion Transport; D007511:Ischemia / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology; D020935:MAP Kinase Signaling System; D017628:Microglia / Q000502:physiology*; D010766:Phosphorylation; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015861:Retinal Neovascularization / Q000178:diet therapy* / Q000503:physiopathology / Q000517:prevention & control; D012178:Retinopathy of Prematurity; D012964:Sodium / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000098854:Kcnj10 Channel
chemical_list: D033961:Adaptor Protein Complex 1; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D053503:Epithelial Sodium Channels; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D017673:Sodium Chloride, Dietary; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004921:Erythropoietin; D000450:Aldosterone; D012964:Sodium
keywords: aldosterone; ion channel