title: Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina.
abstract: OBJECTIVE
  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.
authors: Institut National de la Santé et de la Recherche Médicale U872, Team 17, Physiopathology of Ocular Diseases: Therapeutic Innovations, Paris, France.
authors: Min
authors: M
authors: Zhao
authors: Elodie
authors: E
authors: Bousquet
authors: Fatemeh
authors: F
authors: Valamanesh
authors: Nicolette
authors: N
authors: Farman
authors: Jean-Claude
authors: JC
authors: Jeanny
authors: Frederic
authors: F
authors: Jaisser
authors: Francine F
authors: FF
authors: Behar-Cohen
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005938:Glucocorticoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014222:Triamcinolone Acetonide / Q000494:pharmacology; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism; D000098854:Kcnj10 Channel
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D005938:Glucocorticoids; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D003907:Dexamethasone; D014222:Triamcinolone Acetonide