Mineralocorticoid pathway in retinal health and diseases

Abstract

In the retina, the mineralocorticoid receptor is expressed in retinal and choroidal vessels and in cells from neural and glial origins. Like in the brain, the major ligand of the mineralocorticoid receptor is cortisol, and the mineralocorticoid/glucocorticoid receptor balance regulates the activation of the MR pathway. Experimental mineralocorticoid receptor pathway activation using either pharmacological agents or transgenic manipulation favours retinal and choroidal pathology. In various models of retinal diseases, such as glaucomatous neuropathy, retinopathy of prematurity, ischaemic retinopathies, diabetic retinopathy and choroidal neovascularization, mineralocorticoid receptor antagonism exerts beneficial effects, demonstrating its potential in the treatment of major blinding retinal diseases. But specific formulations are required to optimize the bioavailability of mineralocorticoid receptor antagonists in various compartments of the eye, and molecular biomarkers of mineralocorticoid receptor pathway activation remain to be identified in humans to select patients amenable to clinical trials.

Blood flow in the optic nerve head in patients with primary aldosteronism

“…In the retina, MRs are expressed in retinal and choroidal vessels and in the retinal pigment epithelium (RPE) cells [ 15 , 16 ]. It is speculated that overactivation of the retina/choroidal MR pathway could contribute to the mechanisms of central serous chorioretinopathy (CSC) [ 17 ].…”

Emerging fields for therapeutic targeting of the aldosterone–mineralocorticoid receptor signaling pathway

“…The current evidence derived from experimental studies suggests beneficial effects of MR antagonists or cell‐selective MR gene targeting in mice, involving epithelial cells, neurons, microglia, and endothelial cells of the retina and the choroid. Challenges for the clinical use of MR antagonists in retinal diseases remain as available steroidal compounds do not cross the blood‐retinal barrier (Behar‐Cohen & Zhao, 2022).…”

“…Oxidative stress, oedema, inflammation, and neovascularization are key features of retinal diseases that represent the most common causes of blindness worldwide. In their review article, Behar‐Cohen and Zhao (2022) put together what is known about the consequences of MR activation or inhibition in retinal disease. The current evidence derived from experimental studies suggests beneficial effects of MR antagonists or cell‐selective MR gene targeting in mice, involving epithelial cells, neurons, microglia, and endothelial cells of the retina and the choroid.…”

Novel 1,4-Dihydropyridine Derivatives as Mineralocorticoid Receptor Antagonists

“…For instance, excessive MR activity promotes deleterious cardiovascular and renal remodeling [7,8], both directly and through the modulation of innate and adaptive immune cells [9]. MR has also been implicated in the development of metabolic abnormalities [10,11], inflammatory skin diseases [12], or retinal and choroidal pathology [13]. In addition, MR plays a key role in stress adaptation in the brain, and its dysregulation affects cognition and behavior [14].…”