Aldosterone Exposure Causes Increased Retinal Edema and Severe Retinopathy Following Laser-Induced Retinal Vein Occlusion in Mice

Allingham, Michael J.; Tserentsoodol, Nomingerel; Saloupis, Peter; Mettu, Priyatham S; Cousins, Scott W.

doi:10.1167/iovs.17-23073

Cited by 28 publications

(19 citation statements)

References 28 publications

(43 reference statements)

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“…In this model, aldosterone‐exposed mice demonstrated more severe retinal oedema, intraretinal haemorrhage and severe retinal ischaemia. The blood–retinal barrier was altered with inflammatory cell infiltration, and retinal Müller glial cells showed fluid and ion pump dysfunction (Allingham et al, 2018), suggesting that aldosterone could have penetrated inside the retina in case of retinal vein occlusion.…”

Section: Consequences Of Experimental Mineralocorticoid Receptor Path...mentioning

confidence: 99%

Mineralocorticoid pathway in retinal health and diseases

Zhao

2022

British J Pharmacology

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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.

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Section: Consequences Of Experimental Mineralocorticoid Receptor Path...mentioning

confidence: 99%

Mineralocorticoid pathway in retinal health and diseases

Zhao

2022

British J Pharmacology

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“…GCs act through binding to the glucocorticoid (GR) and the mineralocorticoid receptor (MR), both expressed in various cells in the retina in rodents and in humans, including the RPE [13][14][15][16]. Evidence from animal and cellular models converges to indicate that in the retina, as in other non-classical MR-sensitive tissues, MR pathway overactivation is pathogenic [15][16][17][18][19][20][21] and causes pathogenic features similar to CSCR, a disease that develops due to focal disruption of the RPE barrier function [19]. Indeed, GCs were shown to regulate the RPE functions [22][23][24] and aldosterone to cause RPE/choroid pathology in vivo [21].…”

Section: Introductionmentioning

confidence: 99%

Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium

Canonica

Zhao

Favez

et al. 2021

IJMS

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Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.

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“…Importantly, macular edema secondary to RVO is one of the leading causes of vision loss [33]. The mechanism of macular edema is complex and still unclear [34,35]. Many studies have demonstrated that breakdown of the blood retinal barrier and retinal vascular hyperpermeability are important in the pathophysiologic process of macular edema associated with RVO [8,28].…”

Section: Discussionmentioning

confidence: 99%

Increased Macrophage-like Cell Density in Retinal Vein Occlusion as Characterized by Swept-Source Optical Coherence Tomography Angiography

Wang¹,

Sun²,

Li³

et al. 2022

Preprint

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Objectives: To quantitatively analyze macrophage-like cells (MLCs) at the vitreoretinal interface in retinal vein occlusion (RVO) using swept-source optical coherence tomography angiography (SS-OCTA).Methods: The study included 72 RVO patients, with 43 acute patients and 29 chronic patients. For a normal control, 64 fellow eyes were included. MLCs were visualized in a 5μm en face OCT slab above the vitreoretinal interface centered on the fovea. After semi-automatic binarization and quantification, we evaluated the MLC count and density among groups. We also investigated the MLC density and distribution relative to retinal edema.Results: Morphological changes and congregation of MLCs appeared in RVO eyes. The MLC density of both the acute and chronic groups was significantly higher than that of the control eyes (p<0.001). In the acute group, the MLC density of the edematous region was lower than both the non-edematous region (p<0.001) and the whole image (p<0.01). The MLC density in acute eyes was negatively correlated to central fovea thickness (CFT) (r=-0.352, p<0.05). The MLC density in chronic eyes was positively correlated to CFT and mean retina thickness (MRT) (r=0.406, P<0.05; r=0.412, P<0.05, respectively).Conclusions: SS-OCTA is a viable and simple method for the characterization of MLCs at the vitreoretinal interface. A significant increase in the MLC density in both acute and chronic eyes implicates the activation and recruitment of MLCs in RVO and that the MLC density and distribution can be affected by retinal edema.

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Aldosterone Exposure Causes Increased Retinal Edema and Severe Retinopathy Following Laser-Induced Retinal Vein Occlusion in Mice

Cited by 28 publications

References 28 publications

Mineralocorticoid pathway in retinal health and diseases

Mineralocorticoid pathway in retinal health and diseases

Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium

Increased Macrophage-like Cell Density in Retinal Vein Occlusion as Characterized by Swept-Source Optical Coherence Tomography Angiography

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