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Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology.
Circ Res. 2009 01 02; 104(1):124-33.CircR

Abstract

Blockade of the renin-angiotensin-aldosterone system (RAAS) is being evaluated as a treatment for diabetic retinopathy; however, whether the mineralocorticoid receptor (MR) and aldosterone influence retinal vascular pathology is unknown. We examined the effect of MR antagonism on pathological angiogenesis in rats with oxygen-induced retinopathy (OIR). 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 11beta-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-aldosterone 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.

Authors+Show Affiliations

Department of Immunology, Monash University, Commercial Rd, Prahran, Victoria, Australia, 3004. Jennifer.Wilkinson-Berka@med.monash.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19038868

Citation

Wilkinson-Berka, Jennifer L., et al. "Identification of a Retinal Aldosterone System and the Protective Effects of Mineralocorticoid Receptor Antagonism On Retinal Vascular Pathology." Circulation Research, vol. 104, no. 1, 2009, pp. 124-33.
Wilkinson-Berka JL, Tan G, Jaworski K, et al. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology. Circ Res. 2009;104(1):124-33.
Wilkinson-Berka, J. L., Tan, G., Jaworski, K., Harbig, J., & Miller, A. G. (2009). Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology. Circulation Research, 104(1), 124-33. https://doi.org/10.1161/CIRCRESAHA.108.176008
Wilkinson-Berka JL, et al. Identification of a Retinal Aldosterone System and the Protective Effects of Mineralocorticoid Receptor Antagonism On Retinal Vascular Pathology. Circ Res. 2009 01 2;104(1):124-33. PubMed PMID: 19038868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology. AU - Wilkinson-Berka,Jennifer L, AU - Tan,Genevieve, AU - Jaworski,Kassie, AU - Harbig,Jacqueline, AU - Miller,Antonia G, Y1 - 2008/11/26/ PY - 2008/11/29/pubmed PY - 2009/2/12/medline PY - 2008/11/29/entrez SP - 124 EP - 33 JF - Circulation research JO - Circ Res VL - 104 IS - 1 N2 - Blockade of the renin-angiotensin-aldosterone system (RAAS) is being evaluated as a treatment for diabetic retinopathy; however, whether the mineralocorticoid receptor (MR) and aldosterone influence retinal vascular pathology is unknown. We examined the effect of MR antagonism on pathological angiogenesis in rats with oxygen-induced retinopathy (OIR). 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 11beta-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-aldosterone 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. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/19038868/Identification_of_a_retinal_aldosterone_system_and_the_protective_effects_of_mineralocorticoid_receptor_antagonism_on_retinal_vascular_pathology_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.108.176008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -