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To determine the mechanisms by which the MR and aldosterone may influence retinal angiogenesis; inflammation and glucose-6-phosphate dehydrogenase (G6PD) were evaluated in OIR and cultured bovine retinal endothelial cells (BRECs) and bovine retinal pericytes (BRPs). In OIR, MR antagonism (spironolactone) was antiangiogenic. Aldosterone may mediate the pathogenic actions of MR in the retina, with 11\u03b2-hydroxysteroid dehydrogenase type 2 mRNA being detected and with aldosterone stimulating proliferation and tubulogenesis in BRECs and exacerbating angiogenesis in OIR, which was attenuated with spironolactone. The MR and aldosterone modulated retinal inflammation, with leukostasis and monocyte chemoattractant protein-1 mRNA and protein in OIR being reduced by spironolactone and increased by aldosterone. A reduction in G6PD may be an early response to aldosterone. In BRECs, BRPs, and early OIR, aldosterone reduced G6PD mRNA, and in late OIR, aldosterone increased mRNA for the NAD(P)H oxidase subunit Nox4. A functional retinal MR\u2013aldosterone system was evident with MR expression, translocation of nuclear MR, and aldosterone synthase expression, which was modulated by RAAS blockade. We make the first report that MR and aldosterone influence retinal vasculopathy, which may involve inflammatory and G6PD mechanisms. MR antagonism may be relevant when developing treatments for retinopathies that target the RAAS.<\/jats:p>","DOI":"10.1161\/circresaha.108.176008","type":"journal-article","created":{"date-parts":[[2008,11,26]],"date-time":"2008-11-26T21:57:42Z","timestamp":1227736662000},"page":"124-133","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":152,"title":["Identification of a Retinal Aldosterone System and the Protective Effects of Mineralocorticoid Receptor Antagonism on Retinal Vascular Pathology"],"prefix":"10.1161","volume":"104","author":[{"given":"Jennifer L.","family":"Wilkinson-Berka","sequence":"first","affiliation":[{"name":"From the Department of Immunology, Monash University, Prahran, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Tan","sequence":"additional","affiliation":[{"name":"From the Department of Immunology, Monash University, Prahran, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassie","family":"Jaworski","sequence":"additional","affiliation":[{"name":"From the Department of Immunology, Monash University, Prahran, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Harbig","sequence":"additional","affiliation":[{"name":"From the Department of Immunology, Monash University, Prahran, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia G.","family":"Miller","sequence":"additional","affiliation":[{"name":"From the Department of Immunology, Monash University, Prahran, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-007-9066-0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-9071.2005.01032.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61412-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61411-7"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-68-1-160"},{"key":"e_1_3_3_6_2","first-page":"1450","volume":"36","year":"1995","unstructured":"Berka JL, Stubbs AJ, Wang DZ, DiNicolantonio R, Alcorn D, Campbell DJ, Skinner SL. 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