Glucocorticoids induce retinal toxicity through mechanisms mainly associated with paraptosis.

Détails

ID Serval
serval:BIB_1D28D452A382
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Glucocorticoids induce retinal toxicity through mechanisms mainly associated with paraptosis.
Périodique
Molecular Vision
Auteur⸱e⸱s
Valamanesh F., Torriglia A., Savoldelli M., Gandolphe C., Jeanny J.C., BenEzra D., Behar-Cohen F.
ISSN
1090-0535 (Electronic)
ISSN-L
1090-0535
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
13
Pages
1746-1757
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
PURPOSE: Corticosteroids have recorded beneficial clinical effects and are widely used in medicine. In ophthalmology, besides their treatment benefits, side effects, including ocular toxicity have been observed especially when intraocular delivery is used. The mechanism of these toxic events remains, however, poorly understood. In our present study, we investigated the mechanisms and potential pathways of corticosteroid-induced retinal cell death.
METHODS: Rats were sacrificed 24 h and 8 days after an intravitreous injection of 1 microl (40 microg) of Kenacort Retard. The eyes were processed for ultra structure analysis and detection of activated caspase-3, cytochrome-C, apoptosis-inducing factor (AIF), LEI-L-Dnase II, terminal transferase dUTP nick end labeling (TUNEL), and microtubule-associated protein 1-light chain 3 (MAP-LC3). In vitro, rat retinal pigment epithelial cells (RPE), retinal Müller glial cells (RMG) and human ARPE-19 cells were treated with triamcinolone acetonide (TA) or other glucocorticoids. Cell viability was quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5 phenyltetrazolium bromide test (MTT) assay and cell counts. Nuclei staining, TUNEL assay, annexin-V binding, activated caspase-3 and lactate dehydrogenase (LDH) production characterized cell death. Localization of cytochrome-C, AIF, LEI-and L-Dnase II, and staining with MAP-LC3 or monodansylcadaverine were also carried out. Finally, ARPE-19 cells transfected with AIP-1/Alix were exposed to TA.
RESULTS: In vitro incubation of retinal cell in the presence of corticosteroids induced a specific and dose-dependent reduction of cell viability. These toxic events were not associated with the anti-inflammatory activity of these compounds but depended on the hydro solubility of their formulation. Before cell death, extensive cytoplasmic vacuolization was observed in the retinal pigment epithelial (RPE) cells in vivo and in vitro. The cells however, did not show known caspase-dependent or caspase-independent apoptotic reactions. These intracellular vacuoles were negative for MAP-LC3 but some stained positive for monodansylcadaverine. Furthermore, over expression of AIP-1/Alix inhibited RPE cell death.
CONCLUSIONS: These observations suggest that corticosteroid-induced retinal cell death may be carried out mainly through a paraptosis pathway.
Mots-clé
Adrenal Cortex Hormones/administration & dosage, Adrenal Cortex Hormones/chemistry, Animals, Apoptosis, Autophagy, Cell Death, Cell Survival/drug effects, Cells, Cultured, Cytoplasm/pathology, Dose-Response Relationship, Drug, Humans, Injections, Microscopy, Electron, Necrosis, Neuroglia/drug effects, Pigment Epithelium of Eye/drug effects, Pigment Epithelium of Eye/pathology, Polysorbates/poisoning, Rats, Rats, Inbred Lew, Retina/drug effects, Retina/pathology, Solubility, Triamcinolone Acetonide/poisoning, Vacuoles/pathology, Vitreous Body, Water
Pubmed
Web of science
Création de la notice
27/08/2013 14:35
Dernière modification de la notice
20/08/2019 12:53
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