{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:03:36Z","timestamp":1793261016855,"version":"4.5.0"},"reference-count":107,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["20K09827"],"award-info":[{"award-number":["20K09827"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Aldosterone is one of the main effectors of the renin-angiotensin-aldosterone system (RAAS) along with having roles in hypertension, and cardiovascular and renal diseases. Recent evidence has also shown the presence of an active local RAAS within the human eye. It has been shown that at 12 h after a retinal ischemia-reperfusion injury, there is an upregulation of the protein levels of angiotensin II type 1 receptor (AT1-R) in the retina. Furthermore, at 12 h after reperfusion, there is an increase in reactive oxygen species (ROS) production in the retina that is mediated via an NADPH oxidase pathway. This ischemia-reperfusion injury-induced increase of retinal ROS levels and NADPH oxidase expression can be prevented by the administration of an AT1-R antagonist. This suggests that one of the main retinal ischemic injury pathways is via the local RAAS. It has also been reported that progressive retinal ganglion cell loss and glaucomatous optic nerve degeneration without elevated intraocular pressure occur after administration of local or systemic aldosterone. Elucidation of glaucoma pathogenesis, especially normal-tension glaucoma (NTG) subtype by our current animal model can be used for identifying potential therapeutic targets. Based on these results, we are further evaluating NTG prevalence among primary aldosteronism patients.<\/jats:p>","DOI":"10.3390\/antiox11040610","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T14:55:35Z","timestamp":1647960935000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Retinal Renin-Angiotensin-Aldosterone System: Implications for Glaucoma"],"prefix":"10.3390","volume":"11","author":[{"given":"Kazuyuki","family":"Hirooka","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kiuchi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.survophthal.2008.08.006","article-title":"Risk factors for glaucoma onset and progression","volume":"53","author":"Coleman","year":"2008","journal-title":"Surv. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.survophthal.2009.05.001","article-title":"Understanding the importance of IOP variable in glaucoma: A systematic review","volume":"54","author":"Sultan","year":"2009","journal-title":"Surv. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1001\/archopht.120.10.1268","article-title":"Reduction of intraocular pressure and glaucoma progression: Results from the Early Manifest Glaucoma Trial","volume":"120","author":"Heijl","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Collaborative Normal-Tension Glaucoma Study Group (1998). Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am. J. Ophthalmol., 126, 487\u2013497.","DOI":"10.1016\/S0002-9394(98)00223-2"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1097\/00061198-199906000-00012","article-title":"Vascular dysregulation: A principal risk factor for glaucomatous damage?","volume":"8","author":"Flammer","year":"1999","journal-title":"J. Glaucoma."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/S0039-6257(99)00018-1","article-title":"The role of age and cardiovascular diseases in glaucomatous optic neuropathy","volume":"43","author":"Hayreh","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/S0161-6420(00)00138-X","article-title":"Vascular risk factors for primary open angle glaucoma: The Enga-Neumarkt Study","volume":"107","author":"Bonomi","year":"2000","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0002-9394(01)00964-3","article-title":"Risk factors for progression of visual field abnormalities in normal-tension glaucoma","volume":"131","author":"Drance","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shalaby, W.S., Ahmed, O.M., Waisbourd, M., and Katz, L.J. (2021). A review of potential novel glaucoma therapeutic options independent of intraocular pressure. Surv. Ophthalmol., in press.","DOI":"10.1016\/j.survophthal.2021.12.003"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/eurheartj\/ehr253","article-title":"Therapeutic perspectives in hypertension: Novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches","volume":"32","author":"Unger","year":"2011","journal-title":"Eur. Heart. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s11906-014-0431-2","article-title":"Angiotensin II and vascular injury","volume":"16","author":"Montezano","year":"2014","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.kint.2019.02.030","article-title":"Mineralocorticoid receptor antagonists and kidney diseases: Pathophysiological basis","volume":"96","author":"Girerd","year":"2019","journal-title":"Kidney. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/bs.vh.2018.09.005","article-title":"Aldosterone and myocardial pathology","volume":"109","author":"Cannavo","year":"2019","journal-title":"Vitam. Horm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/MED.0b013e3283391989","article-title":"Aldosterone and inflammation","volume":"17","author":"Gilbert","year":"2010","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"594","DOI":"10.2174\/157016111796642689","article-title":"Aldosterone, from (patho)physiology to treatment in cardiovascular and renal damage","volume":"9","author":"Waanders","year":"2011","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jacc.2007.10.027","article-title":"Renin inhibition in hypertension","volume":"51","author":"Gradman","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1161\/HYPERTENSIONAHA.108.110932","article-title":"Renin inhibition by aliskiren prevents atherosclerosis progression: Comparison with irbesartan, atenolol, and amlodipine","volume":"51","author":"Nussberger","year":"2008","journal-title":"Hypertension"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1161\/ATVBAHA.108.182519","article-title":"Dynamic observation of mechanically-injured mouse femoral artery reveals an antiinflammatory effect of renin inhibitor","volume":"29","author":"Ino","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107680","DOI":"10.1016\/j.exer.2019.05.020","article-title":"The renin angiotensin aldosterone system and its therapeutic targets","volume":"186","author":"Bovee","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.amjcard.2004.01.007","article-title":"Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension","volume":"93","author":"Williams","year":"2004","journal-title":"Am. J. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1161\/01.HYP.31.1.451","article-title":"Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats","volume":"31","author":"Rocha","year":"1998","journal-title":"Hypertension"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1161\/01.HYP.13.2.115","article-title":"Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats","volume":"13","author":"Stier","year":"1989","journal-title":"Hypertension"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/ajh\/4.8.680","article-title":"Therapeutic benefit of captopril in salt-loaded stroke-prone spontaneously hypertensive rats is independent of hypotensive effect","volume":"4","author":"Stier","year":"1991","journal-title":"Am. J. Hypertens."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1161\/01.HYP.33.1.232","article-title":"Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats","volume":"33","author":"Rocha","year":"1999","journal-title":"Hypertension"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1161\/01.STR.28.9.1821","article-title":"The role of blood pressure and aldosterone in the production of hemorrhagic stroke in captopril-treated hypertensive rats","volume":"28","author":"MacLeod","year":"1997","journal-title":"Stroke"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1172\/JCI118867","article-title":"Role of aldosterone in the remnant kidney model in the rat","volume":"98","author":"Greene","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/147323000102900103","article-title":"Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in essential hypertensive patients with left ventricular hypertrophy","volume":"29","author":"Sato","year":"2001","journal-title":"J. Int. Med. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-1-4615-5385-4_4","article-title":"Regulation and role of myocardial collagen matrix remodeling in hypertensive heart disease","volume":"432","author":"Funck","year":"1997","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1161\/01.HYP.33.4.981","article-title":"Angiotensin AT1 receptor subtype as a cardiac target of aldosterone: Role in aldosterone-salt-induced fibrosis","volume":"33","author":"Robert","year":"1999","journal-title":"Hypertension"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1161\/01.CIR.104.2.137","article-title":"Aldosterone induces angiotensin-converting-enzyme gene expression in cultured neonatal rat cardiocytes","volume":"104","author":"Harada","year":"2001","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1161\/01.HYP.35.6.1183","article-title":"Angiotensin II and the heart: On the intracrine renin-angiotensin system","volume":"35","author":"Danser","year":"2000","journal-title":"Hypertension"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0303-7207(00)00406-8","article-title":"Control of renin secretion from adrenal gland in transgenic Ren-2 and normal rats","volume":"173","author":"Rong","year":"2001","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_34","first-page":"E639","article-title":"Renin in thymus, gut, hindlimb, and adrenal of (mRen-2)27 and normal rats: Secretion and content studies","volume":"277","author":"Rong","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/978-1-4899-0952-7_27","article-title":"The ovarian renin-angiotensin system. A paracrine-intracrine regulator of ovarian function","volume":"377","author":"Pepperell","year":"1995","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_36","first-page":"1008","article-title":"Angiotensin levels in the eye","volume":"35","author":"Danser","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1210\/endo-126-3-1673","article-title":"Identification and quantification of renin and prorenin in the bovine eye","volume":"126","author":"Deinum","year":"1990","journal-title":"Endocrinology"},{"key":"ref_38","first-page":"1450","article-title":"Renin-containing M\u00fcller cells of the retina display endocrine features","volume":"36","author":"Berka","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/bjo.80.2.159","article-title":"Demonstration of rennin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: Evidence for an intraocular rennin-angiotensin system","volume":"80","author":"Wagner","year":"1996","journal-title":"Br. J. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1210\/jcem-68-1-160","article-title":"Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy","volume":"68","author":"Danser","year":"1989","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1161\/HYPERTENSIONAHA.111.188136","article-title":"Neovascularization is attenuated with aldosterone synthase inhibition in rats with retinopathy","volume":"59","author":"Deliyanti","year":"2012","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1161\/CIRCRESAHA.108.176008","article-title":"Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology","volume":"104","author":"Tan","year":"2009","journal-title":"Circ. Res."},{"key":"ref_43","first-page":"269","article-title":"Glaucoma, capillaries and pericytes 3. Peptide hormone binding and influence on pericytes","volume":"210","author":"Davis","year":"1996","journal-title":"Ophthalmologica"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1100\/tsw.2009.70","article-title":"Angiotensin-(1-7) and its effects in the kidney","volume":"9","author":"Dilauro","year":"2009","journal-title":"Sci. World J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/MNH.0b013e328341164a","article-title":"Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal diseases","volume":"20","author":"Tikellis","year":"2011","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s00417-015-2952-z","article-title":"The expression of Mas-receptor of the renin-angiotensin system in the human eye","volume":"253","author":"Vaajanen","year":"2015","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"ref_47","first-page":"1443","article-title":"Expression and cellular localization of the Mas receptor in the adult and developing mouse retina","volume":"20","author":"Prasad","year":"2014","journal-title":"Mol. Vis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/mt.2011.155","article-title":"ACE2 and Ang-(1-7) confer protection against development of diabetic retinopathy","volume":"20","author":"Verma","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.ajpath.2016.01.023","article-title":"Adeno-associated virus overexpression of angiotensin-converting enzyme-2 reverses diabetic retinopathy in type 1 diabetes in mice","volume":"186","author":"Dominguer","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1038\/mt.2014.179","article-title":"Oral delivery of ACE2\/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis","volume":"22","author":"Shil","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1167\/iovs.14-13883","article-title":"Angiotensin-converting enzyme-2 (ACE2) activator diminazene aceturate ameliorates endotoxin-induced uveitis in mice","volume":"55","author":"Qiu","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1167\/iovs.06-1024","article-title":"Angiotensin II and its receptor subtypes in the human retina","volume":"48","author":"Senanayake","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/0002-9394(88)90063-3","article-title":"Use of an angiotensin converting enzyme inhibitor in ocular hypertension and primary open-angle glaucoma","volume":"105","author":"Constad","year":"1988","journal-title":"Am. J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0140-6736(97)06209-0","article-title":"Effect of lisinopril on progression of retinopathy in normotensive people with type I diabetes. The EUCLID study group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus","volume":"351","author":"Chaturvedi","year":"1998","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1172\/JCI61427","article-title":"Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy","volume":"122","author":"Zhao","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1097\/IAE.0000000000000614","article-title":"Spironolactone for nonresolving central serous chorioretinopathy: A randomized controlled crossover study","volume":"35","author":"Bousquet","year":"2015","journal-title":"Retina"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41467-018-08125-6","article-title":"Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration","volume":"10","author":"Zhao","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.preteyeres.2003.12.001","article-title":"Retinal ischemia: Mechanisms of damage and potential therapeutic strategies","volume":"23","author":"Osborne","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1016\/S0039-6257(99)00044-2","article-title":"Neuroprotection in relation to retinal ischemia and relevance to glaucoma","volume":"43","author":"Osborne","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1001\/archopht.1975.01010020934002","article-title":"Retinal ischemia in diabetic retinopathy","volume":"93","author":"Bresnick","year":"1975","journal-title":"Arch. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1523\/JNEUROSCI.07-02-00369.1987","article-title":"Ionic dependence of glutamate neurotoxicity","volume":"7","author":"Choi","year":"1987","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/0166-2236(88)90200-7","article-title":"Calcium-mediated neurotoxicity: Relationship to specific channel types and role in ischemic damage","volume":"11","author":"Choi","year":"1988","journal-title":"Trends Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1001\/archopht.1989.01070010349021","article-title":"Excitotoxins: A possible new mechanism for the pathogenesis of ischemic retinal damage","volume":"107","author":"Bresnick","year":"1989","journal-title":"Arch. Ophthalmol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1471-4159.1992.tb08912.x","article-title":"Glutamate release in experimental ischaemia of the retina: An approach using microdialysis","volume":"59","author":"Dias","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1167\/iovs.09-4107","article-title":"Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin II type 1 receptor","volume":"51","author":"Fukuda","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1167\/iovs.05-1018","article-title":"Neuroprotective effects of D-allose against retinal ischemia-reperfusion injury","volume":"47","author":"Hirooka","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.exer.2014.03.011","article-title":"Effect of the Renin inhibitor aliskiren against retinal ischemia-reperfusion injury","volume":"122","author":"Tenkumo","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.exer.2011.12.012","article-title":"Activation of the aldosterone\/mineralocorticoid receptor system and protective effects of mineralocorticoid receptor antagonism in retinal ischemia- reperfusion injury","volume":"96","author":"Liu","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1167\/iovs.11-9167","article-title":"Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels","volume":"53","author":"Fujita","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0079-6123(08)01134-5","article-title":"Targeting excitotoxic\/free radical signaling pathways for therapeutic intervention in glaucoma","volume":"173","author":"Seki","year":"2008","journal-title":"Prog. Brain Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/cdd.2013.91","article-title":"Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma","volume":"20","author":"Namekata","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1167\/iovs.16-21001","article-title":"The relationship between the renin-angiotensin\u2013aldosterone system and NMDA receptor-mediated signal and the prevention of retinal ganglion cell death","volume":"58","author":"Kobayashi","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e711","DOI":"10.1038\/cddis.2013.240","article-title":"Aldosterone: A mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma","volume":"4","author":"Nitta","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"F1065","DOI":"10.1152\/ajprenal.00147.2007","article-title":"Aldosterone promotes proximal tubular cell apoptosis: Role of oxidative stress","volume":"293","author":"Patni","year":"2007","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"F73","DOI":"10.1152\/ajprenal.00435.2007","article-title":"Aldosterone induces mesangial cell apoptosis both in vivo and in vitro","volume":"295","author":"Mathew","year":"2008","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1291\/hypres.31.363","article-title":"Aldosterone nongenomically produces NADPH oxidase-dependent reactive oxygen species and induces myocyte apoptosis","volume":"31","author":"Hayashi","year":"2008","journal-title":"Hypertens. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1470320318795001","article-title":"Elevated plasma aldosterone levels is associated with a reduction in retinal ganglion cell survival","volume":"19","author":"Takasago","year":"2018","journal-title":"J. Renin Angiotensin. Aldosterone. Syst."},{"key":"ref_78","first-page":"774","article-title":"Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis","volume":"36","author":"Quigley","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10384-018-0595-4","article-title":"Gene expression changes in the retina after systemic administration of aldosterone","volume":"62","author":"Ono","year":"2018","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.preteyeres.2006.07.003","article-title":"Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences","volume":"25","author":"Tezel","year":"2006","journal-title":"Prog. Retin. Eye. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.4161\/auto.36076","article-title":"Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells","volume":"10","author":"Lin","year":"2014","journal-title":"Autophagy"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1476-5381.2012.02194.x","article-title":"Aldosterone affects blood flow and vascular tone regulated by endothelium-derived NO: Therapeutic implications","volume":"168","author":"Toda","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.mce.2003.10.024","article-title":"Aldosterone-induced vasculopathy","volume":"217","author":"Struthers","year":"2004","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1210\/en.2006-0965","article-title":"A direct effect of aldosterone on endothelin-1 gene expression in vivo","volume":"148","author":"Wong","year":"2007","journal-title":"Endocrinology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1167\/iovs.15-18358","article-title":"Local modulation of retinal vein tone","volume":"57","author":"Yu","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1161\/01.HYP.0000171184.84077.80","article-title":"Aldosterone nongenomically worsens ischemia via protein kinase C-dependent pathway in hypoperfused canine hearts","volume":"46","author":"Fujita","year":"2005","journal-title":"Hypertension"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0021-9150(02)00363-5","article-title":"Aldosterone induces contraction of the resistance arteries in man","volume":"166","author":"Romagni","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wada, Y., Higashide, T., Sakaguchi, K., Nagata, A., Hirooka, K., and Sugiyama, K. (2022). Compromised blood flow in the optic nerve head after systemic administration of aldosterone in rats. A possible rat model of retinal ganglion cell loss. Curr. Eye Res., online ahead of print.","DOI":"10.1080\/02713683.2022.2029907"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/hr.2009.34","article-title":"Japanese Society of Hypertension Committee. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009)","volume":"32","author":"Ogihara","year":"2009","journal-title":"Hypertens. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.HYP.0000040261.30455.B6","article-title":"Hyperaldosteronism among black and white subjects with resistant hypertension","volume":"40","author":"Calhoun","year":"2002","journal-title":"Hypertension"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/sj.jhh.1001554","article-title":"Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region","volume":"17","author":"Strauch","year":"2003","journal-title":"J. Hum. Hypertens."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1161\/01.HYP.0000079505.25750.11","article-title":"Primary aldosteronism and hypertensive diseases","volume":"42","author":"Mosso","year":"2003","journal-title":"Hypertension"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/j.jacc.2017.01.052","article-title":"Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice","volume":"69","author":"Monticone","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2147\/IBPC.S13783","article-title":"Mineralocorticoid receptor antagonists: Emerging roles in cardiovascular medicine","volume":"6","author":"Funder","year":"2013","journal-title":"Integr. Blood Press. Control"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1097\/HJH.0000000000001251","article-title":"Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism","volume":"35","author":"Murata","year":"2017","journal-title":"J. Hypertens."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1001\/archinternmed.2007.33","article-title":"Cardiovascular outcomes in patients with primary aldosteronism after treatment","volume":"168","author":"Catena","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.jacc.2005.01.015","article-title":"Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism","volume":"45","author":"Milliez","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1210\/jc.2013-2805","article-title":"Long-term cardio- and cerebrovascular events in patients with primary aldosteronism","volume":"98","author":"Mulatero","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1161\/01.HYP.0000230444.01215.6a","article-title":"Renal damage in primary aldosteronism: Results of the PAPY Study","volume":"48","author":"Rossi","year":"2006","journal-title":"Hypertension"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1210\/jc.2008-1851","article-title":"Risk factors associated with a low glomerular filtration rate in primary aldosteronism","volume":"94","author":"Reincke","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1002\/jbmr.1660","article-title":"Bone involvement in aldosteronism","volume":"27","author":"Salcuni","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0161-6420(95)31054-8","article-title":"Primary open-angle glaucoma, intraocular pressure, and systemic blood pressure in the general elderly population. The Rotterdam Study","volume":"102","author":"Dielemans","year":"1995","journal-title":"Ophthalmology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/00061198-200408000-00010","article-title":"Open-angle glaucoma and systemic hypertension: The blue mountains eye study","volume":"13","author":"Mitchell","year":"2004","journal-title":"J. Glaucoma"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1001\/archopht.1995.01100070092031","article-title":"Risk factors for open-angle glaucoma. The Barbados Eye Study","volume":"113","author":"Leske","year":"1995","journal-title":"Arch. Ophthalmol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1001\/archopht.120.7.954","article-title":"Incident open-angle glaucoma and blood pressure","volume":"120","author":"Leske","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.peptides.2012.04.008","article-title":"The retinal renin-angiotensin system: Roles of angiotensin II and aldosterone","volume":"36","author":"Agrotis","year":"2012","journal-title":"Peptides"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"107788","DOI":"10.1016\/j.exer.2019.107788","article-title":"Aldosterone as a mediator of severity in retinal vascular diseases: Evidence and potential mechanisms","volume":"188","author":"Allingham","year":"2019","journal-title":"Exp. Eye Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/4\/610\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:41:13Z","timestamp":1760136073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/4\/610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,22]]},"references-count":107,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["antiox11040610"],"URL":"https:\/\/doi.org\/10.3390\/antiox11040610","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,22]]}}}