Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina.

Details

Serval ID
serval:BIB_054D44623049
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina.
Journal
Investigative Ophthalmology and Visual Science
Author(s)
Zhao M., Bousquet E., Valamanesh F., Farman N., Jeanny J.C., Jaisser F., Behar-Cohen F.F.
ISSN
1552-5783 (Electronic)
ISSN-L
0146-0404
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
52
Number
9
Pages
6340-6347
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Abstract
PURPOSE: Glucocorticoids are used to treat macular edema, although the mechanisms underlying this effect remain largely unknown. The authors have evaluated in the normal and endotoxin-induced uveitis (EIU) rats, the effects of dexamethasone (dex) and triamcinolone acetonide (TA) on potassium channel Kir4.1 and aquaporin-4 (AQP4), the two main retinal Müller glial (RMG) channels controlling retinal fluid movement.
METHODS: Clinical as well as relatively low doses of dex and TA were injected in the vitreous of normal rats to evaluate their influence on Kir4.1 and AQP4 expression 24 hours later. The dose-dependent effects of the two glucocorticoids were investigated using rat neuroretinal organotypic cultures. EIU was induced by footpad lipopolysaccharide injection, without or with 100 nM intraocular dex or TA. Glucocorticoid receptor and channel expression levels were measured by quantitative PCR, Western blot, and immunohistochemistry.
RESULTS: The authors found that dex and TA exert distinct and specific channel regulations at 24 hours after intravitreous injection. Dex selectively upregulated Kir4.1 (not AQP4) in healthy and inflamed retinas, whereas TA induced AQP4 (not Kir4.1) downregulation in normal retina and upregulation in EIU. The lower concentration (100 nM) efficiently regulated the channels. Moreover, in EIU, an inflammatory condition, the glucocorticoid receptor was downregulated in the retina, which was prevented by intravitreous injections of the low concentration of dex or TA.
CONCLUSIONS: The results show that dex and TA are far from being equivalent to modulate RMG channels. Furthermore, the authors suggest that low doses of glucocorticoids may have antiedematous effects on the retina with reduced toxicity.
Keywords
Animals, Aquaporin 4/metabolism, Blotting, Western, Dexamethasone/pharmacology, Dose-Response Relationship, Drug, Female, Fluorescent Antibody Technique, Indirect, Glucocorticoids/pharmacology, Immunohistochemistry, Intravitreal Injections, Potassium Channels, Inwardly Rectifying/metabolism, Rats, Rats, Inbred Lew, Retina/drug effects, Retina/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Triamcinolone Acetonide/pharmacology, Uveitis/drug therapy, Uveitis/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
22/08/2013 14:08
Last modification date
20/08/2019 12:27
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