See related article, pages 124–133 Every so often, a study emerges that is refreshing, enlightening, and provocative and that has major clinical significance. Such is the study by Wilkinson-Berka et al1 in this issue of Circulation Research , which challenges the widely held belief that adrenal-derived aldosterone is a hormone that simply regulates volume and sodium balance. Here, we learn that similar to what has been suggested in the heart, brain, and vasculature,2 the eye has a dynamic aldosterone–mineralocorticoid receptor (MR) system that plays an important pathophysiological role in the development of retinal vasculopathy. Angiogenic ocular conditions, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, are the leading causes of irreversible vision loss in developed countries.3,4 Pathological processes contributing to visual loss in these conditions include microaneurysms, hemorrhages, and exudates from new and poorly developed vessels, retinal detachment caused by fibrosis, and neovascular glaucoma, with a resultant increase in intraocular pressure. Exact mechanisms for the development of retinopathy remain elusive, but ischemic changes in vascular permeability, inflammation, and growth factor–induced angiogenesis are fundamental pathological features. Among the many factors that have been implicated in vascular permeability and angiogenesis is vascular endothelial growth factor (VEGF), which signals through protein kinase C, mitogen-activated protein kinases, and reactive oxygen species (ROS) through VEGF receptor 1 (fms-like tyrosine kinase-1) and VEGF receptor 2 (fetal liver kinase-1).3,5 VEGF expression is increased by glucose, advanced glycation end products, transforming growth factor-β, and insulin-like growth factor-1, all of which are modulated by the renin–angiotensin–aldosterone system.5,6 Blocking effects of VEGF with intravitreal anti-VEGF drugs such as pegaptanib, ranibizumab, and bevacizumab modify vasoproliferation and hence prevent retinal neovascularization.7 However, although this treatment provides some benefits, it does not always prevent progression of the disease.7 Moreover, VEGF is pleiotropic affecting …