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(Circulation Research. 2009;104:124.)
© 2009 American Heart Association, Inc.

Integrative Physiology

Identification of a Retinal Aldosterone System and the Protective Effects of Mineralocorticoid Receptor Antagonism on Retinal Vascular Pathology

Jennifer L. Wilkinson-Berka, Genevieve Tan, Kassie Jaworski, Antonia G. Miller

From the Department of Immunology, Monash University, Prahran, Victoria, Australia.

Correspondence to Associate Professor Jennifer L. Wilkinson-Berka, Department of Immunology, Monash University, Commercial Rd, Prahran, Victoria, Australia, 3004. E-mail Jennifer.Wilkinson-Berka{at}med.monash.edu.au

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 11β-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.

Key Words: aldosterone • mineralocorticoid receptor • retina • angiogenesis • inflammation

Related Article:

A New Look at the Eye: Aldosterone and Mineralocorticoid Receptors As Novel Targets in Retinal Vasculopathy

Rhian M. Touyz and Glaucia E. Callera
Circ. Res. 2009 104: 9-11. [Extract] [Full Text] [PDF]

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				R. M. Touyz and G. E. Callera A New Look at the Eye: Aldosterone and Mineralocorticoid Receptors As Novel Targets in Retinal Vasculopathy Circ. Res., January 2, 2009; 104(1): 9 - 11. [Full Text] [PDF]