Effect of acute and chronic aldosterone exposure on the retinal pigment epithelium-choroid complex in rodents

Canonica, Jérémie; Mehanna, Chadi; Bonnard, Benjamin; Jonet, Laurent; Gélizé, Emmanuelle; Jaı̈s, Jean-Philippe; Jaisser, Frédéric; Zhao, Min; Béhar-Cohen, Francine

doi:10.1016/j.exer.2019.107747

Cited by 26 publications

(33 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism by which endogenous corticoids could contribute to the development of PPE is unclear. Although glucocorticoids have strong anti‐inflammatory and immunosuppressive effects, high‐dose cortisol, which has a similar affinity for the gluco‐ and mineralocorticoid receptors, can activate the mineralocorticoid pathway, causing oxidative stress and inflammatory damage to the RPE/choroid complex (Canonica et al 2019) and pachychoroid features, in the absence of subretinal fluid, have been recently described in an animal model chronically exposed to systemic aldosterone due to uninephrectomy, aldosterone and salt exposure (Canonica et al 2019). It could thus be assumed that the ocular phenotype of patients with Cushing syndrome, like their cardiovascular complications, could be related to the activation of the renin–angiotensin–aldosterone and mineralocorticoid pathways (Nieman 2019).…”

Section: Discussionmentioning

confidence: 99%

Choroidal imaging in patients with Cushing syndrome

Eymard

Gerardy

Bouys

et al. 2020

Acta Ophthalmologica

Self Cite

View full text Add to dashboard Cite

Aims Glucocorticoid intake is a well‐established risk factor for central serous chorioretinopathy that belongs to the pachychoroid spectrum disease (PSD). The study aimed to assess the prevalence of PSD and analyse the choroidal phenotype in patients with Cushing syndrome. Methods A cross‐sectional study was performed in Ophtalmopôle hôpital Cochin, Paris, France, with a systematic evaluation of hospitalized patients with Cushing syndrome, between November 2017 and July 2018. 56 eyes from 28 Cushing syndrome patients and 56 eyes of 28 age and gender‐matched, and close spherical equivalent healthy participants were included. All patients underwent a complete ophthalmic examination including Enhanced‐Depth Imaging (EDI)‐Optical Coherence Tomography (OCT). Measures of subfoveal, 1000 µm nasal and 1000 µm temporal choroidal thicknesses were realized, and the presence of choroidal pachyvessels was evaluated. Hormonal tests evaluated the corticotropic axis. Results The number of eyes with PSD was significantly higher in Cushing syndrome patients as compared to controls (21.4% versus 3.6%, p = 0.004). In Cushing patients’ eyes, 17.9% had a pachychoroid pigment epitheliopathy (PPE) and 3.6% had a polypoidal choroidal vasculopathy. Pachyvessels were more common in Cushing syndrome patients than in healthy subjects (71.4% versus 42.9%, p = 0.002). Mean subfoveal choroidal thickness was 331 ± 110 µm in Cushing patients, with no statistical difference between the two groups. There was no correlation between choroidal thickness and urinary and salivary cortisol levels. Conclusion Patients with Cushing syndrome have a higher prevalence of PDS. An ophthalmologic specialized follow‐up of these patients with EDI‐OCT could detect chorioretinal abnormalities and adapt the surveillance of these patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Choroidal imaging in patients with Cushing syndrome

Eymard

Gerardy

Bouys

et al. 2020

Acta Ophthalmologica

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cortisol was found to significantly influence the expression of specific steroid-responsive genes (PER1, GILZ-1 & FKBP5), however aldosterone did not have the same effect. More recently the transcriptomic regulation of the RPE-choroid complex in rats was evaluated following intravitreal injection of high dose aldosterone (Canonica et al 2019). A uninephrectomy/aldosterone/salt model was also created in wild-type C57BL/6 mice.…”

Section: The Corticosteroid Hypothesis and Information From Cell Biology Studiesmentioning

confidence: 99%

Central serous chorioretinopathy: An update on risk factors, pathophysiology and imaging modalities

Kaye

Chandra

Sheth

et al. 2020

Progress in Retinal and Eye Research

158

216

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

“…In the first part of this study, we confirmed that MTRN is a mineralocorticoid target gene. Indeed, in our previous study, we showed that antagonism of the mineralocorticoid receptor (MR) pathway had anti-angiogenic effect in the laser-induced CNV model in rodents and that this effect was unrelated to VEGF, but rather mediated by decorin [13] and by other proteins, up-regulated by MR, and detected in a transcriptomic study, including MTRN [11,13]. Aldosterone, a specific MR agonist, significantly down-regulated MTRN in the retina in vivo, whilst spironolactone rather increased its expression as compared to aldosterone in the RPE/choroid complex.…”

Section: Discussionmentioning

confidence: 99%

“…On the RPE flat-mount, RPE cells are well delineated by phalloidin staining and MTRN appears as dots in the cytoplasm, but also located in the nuclei of cells (Figure 1e). Using RT-PCR, we show that Mtrn is expressed in the rat neural retina and in the RPE/ choroid complex and that intravitreous aldosterone injection significantly reduces Mtrn expression in the neural retina at 24 h (p < 0.001) [11]. Conversely, spironolactone up-regulates Mtrn expression in the RPE (p < 0.05) as compared to aldosterone (Figure 1f).…”

Section: Mtrn Is Widely Distributed In the Rat Neural Retina And In The Retinal Pigment Epithelium And Its Expression Is Regulated By Minmentioning

confidence: 93%

“…GCs bind to the glucocorticoid (GR) and the mineralocorticoid receptor (MR), both expressed in various retinal and choroidal cells including vascular endothelial cells and retinal pigment epithelium (RPE) [8,9]. In the retina and choroid, GR pathway activation is anti-inflammatory, anti-edematous [6], but MR pathway overactivation causes inflammation, oxidative stress, and choroidal pathology [8,[10][11][12]. Using transgenic approaches, we previously showed that MR invalidation in vascular endothelial cells prevented laserinduced CNV and that pharmacologic MR antagonists exerted anti-inflammatory effects and anti-angiogenic effects [13].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Meteorin Is a Novel Therapeutic Target for Wet Age-Related Macular Degeneration

Delaunay

Sellam

Dinet

et al. 2021

JCM

Self Cite

View full text Add to dashboard Cite

The aim of this study was to evaluate the potential anti-angiogenic effect of MTRN (meteorin) in the laser-induced CNV rat model and explore its mechanisms of action. MTRN, thrompospondin-1, glial cell markers (GFAP, vimentin), and phalloidin were immuno-stained in non-human primate flat-mounted retinas and human retina cross sections. The effect of MTRN at different doses and time points was evaluated on laser-induced CNV at 14 days using in vivo fluorescein angiography and ex vivo quantification of CNV. A pan transcriptomic analysis of the retina and the RPE/choroid complex was used to explore MTRN effects mechanisms. In human retina, MTRN is enriched in the macula, expressed in and secreted by glial cells, and located in photoreceptor cells, including in nuclear bodies. Intravitreal MTRN administered preventively reduced CNV angiographic scores and CNV size in a dose-dependent manner. The highest dose, administered at day 7, also reduced CNV. MTRN, which is regulated by mineralocorticoid receptor modulators in the rat retina, regulates pathways associated with angiogenesis, oxidative stress, and neuroprotection. MTRN is a potential novel therapeutic candidate protein for wet AMD.

show abstract

Effect of acute and chronic aldosterone exposure on the retinal pigment epithelium-choroid complex in rodents

Cited by 26 publications

References 44 publications

Choroidal imaging in patients with Cushing syndrome

Choroidal imaging in patients with Cushing syndrome

Central serous chorioretinopathy: An update on risk factors, pathophysiology and imaging modalities

Meteorin Is a Novel Therapeutic Target for Wet Age-Related Macular Degeneration

Contact Info

Product

Resources

About