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

Détails

ID Serval
serval:BIB_7B399C2FD129
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effect of acute and chronic aldosterone exposure on the retinal pigment epithelium-choroid complex in rodents.
Périodique
Experimental eye research
Auteur⸱e⸱s
Canonica J., Mehanna C., Bonnard B., Jonet L., Gelize E., Jais J.P., Jaisser F., Zhao M., Behar-Cohen F.
ISSN
1096-0007 (Electronic)
ISSN-L
0014-4835
Statut éditorial
Publié
Date de publication
10/2019
Peer-reviewed
Oui
Volume
187
Pages
107747
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Preclinical and clinical evidences show that aldosterone and/or mineralocorticoid receptor (MR) over-activation by glucocorticoids can be deleterious to the retina and to the retinal pigment epithelium (RPE)-choroid complex. However, the exact molecular mechanisms driving these effects remain poorly understood and pathological consequences of chronic exposure of the retina and RPE/choroid to aldosterone have not been completely explored. We aimed to decipher the transcriptomic regulation in the RPE-choroid complex in rats in response to acute intraocular aldosterone injection and to explore the consequences of systemic chronic aldosterone exposure on the morphology and the gene regulation in RPE/choroid in mice. High dose of aldosterone (100 nM) was intravitreously injected in Lewis rat eyes in order to yield an aldosterone dose able to induce a molecular response at the apical side of the RPE-choroid complex. The posterior segment morphology was evaluated in vivo using optical coherence tomography (OCT) before and 24 h after aldosterone injection. Rat RPE-choroid complexes were used for RNA sequencing and analysis. Uninephrectomy/aldosterone/salt (NAS) model was created in wild-type C57BL/6 mice. After 6 weeks, histology of mouse posterior segments were observed ex vivo. Gene expression in the RPE-choroid complex was analyzed using quantitative PCR. Acute intravitreous injection of aldosterone induced posterior segment inflammation observed on OCT. RNA sequencing of rat RPE-choroid complexes revealed up-regulation of pathways involved in inflammation, oxidative stress and RNA procession, and down-regulation of genes involved in synaptic activity, muscle contraction, cytoskeleton, cell junction and transporters. Chronic aldosterone/salt exposure in NAS model induces retinal edema, choroidal vasodilation and RPE cell dysfunction and migration. Quantitative PCR showed deregulation of genes involved in inflammatory response, oxidative stress, particularly the NOX pathway, angiogenesis and cell contractility. Both rodent models share some common phenotypes and molecular regulations in the RPE-choroid complex that could contribute to pachychoroid epitheliopathy in humans. The difference in inflammatory status relies on different intraocular or systemic route of aldosterone administration and on the different doses of aldosterone exposed to the RPE-choroid complex.
Mots-clé
Acute Disease, Aldosterone/pharmacology, Animals, Blood Pressure/drug effects, Cell Movement, Choroid/drug effects, Choroid/metabolism, Choroid/pathology, Choroid Diseases/chemically induced, Choroid Diseases/diagnosis, Chronic Disease, Disease Models, Animal, Eye Proteins/genetics, Gene Expression Regulation/physiology, Intravitreal Injections, Male, Mice, Mice, Inbred C57BL, Nephrectomy, Papilledema/chemically induced, Papilledema/diagnosis, Rats, Rats, Inbred Lew, Real-Time Polymerase Chain Reaction, Retinal Pigment Epithelium/drug effects, Retinal Pigment Epithelium/metabolism, Retinal Pigment Epithelium/pathology, Sequence Analysis, RNA, Tomography, Optical Coherence, Inflammation, Mineralocorticoid receptor, RNA sequencing, Retina
Pubmed
Web of science
Création de la notice
19/08/2019 16:34
Dernière modification de la notice
06/03/2020 6:20
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