Protection of Glial Müller Cells by Dexamethasone in a Mouse Model of Surgically Induced Blood-Retinal Barrier Breakdown.

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  • Additional Information
    • Source:
      Publisher: Association For Research In Vision And Ophthalmology (Arvo) Country of Publication: United States NLM ID: 7703701 Publication Model: Print Cited Medium: Internet ISSN: 1552-5783 (Electronic) Linking ISSN: 01460404 NLM ISO Abbreviation: Invest Ophthalmol Vis Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Brookline Ma : Association For Research In Vision And Ophthalmology (Arvo)
      Original Publication: St. Louis, Mosby.
    • Subject Terms:
      Anti-Inflammatory Agents/*pharmacology ; Blood-Retinal Barrier/*drug effects ; Dexamethasone/*pharmacology ; Ependymoglial Cells/*drug effects ; Retinal Degeneration/*drug therapy; Animals ; Aquaporin 4/metabolism ; Blood-Retinal Barrier/metabolism ; Blotting, Western ; DNA-Binding Proteins/metabolism ; Disease Models, Animal ; Dystrophin/metabolism ; Ependymoglial Cells/metabolism ; Heat Shock Transcription Factors ; Immunohistochemistry ; Intravitreal Injections ; Mice ; Mice, Inbred C57BL ; Potassium Channels, Inwardly Rectifying/metabolism ; Retina/drug effects ; Retina/metabolism ; Retinal Degeneration/metabolism ; Transcription Factors/metabolism
    • Abstract:
      Purpose: Breakdown of the inner blood-retinal barrier (iBRB) occurs in many retinal disorders and may cause retinal edema often responsible for vision loss. Dexamethasone is used in clinical practice to restore iBRB. The aim of this study was to characterize the impact of a surgically induced iBRB breakdown on retinal homeostatic changes due to dystrophin Dp71, aquaporin-4 (AQP4), and Kir4.1 alterations in Müller glial cells (MGC) in a mouse model. The protective effect of dexamethasone was assessed in this model. Moreover, retinal explants were used to control MGC exposure to a hypoosmotic solution containing barium.
      Methods: Partial lens surgery was performed in C57BL6/J mice. Dystrophin Dp71, AQP4, and Kir4.1 expression was analyzed by quantitative RT-PCR, Western blot, and immunohistochemistry. Twenty-four hours after surgery, mice received a single intravitreal injection of dexamethasone or of vehicle.
      Results: After partial lens surgery, iBRB permeability increased while Dp71 and AQP4 were downregulated and Kir4.1 was delocalized. These effects were partially prevented by dexamethasone injection. In the retinal explant model, MGC were swollen and Dp71, AQP4, and Kir4.1 were downregulated after exposure to a hypoosmotic solution containing barium, but not in the presence of dexamethasone. Heat shock factor protein 1 (HSF1) was overexpressed in dexamethasone-treated retinas.
      Conclusions: Partial lens surgery induces iBRB breakdown and molecular changes in MGC, including a downregulation of Dp71 and AQP4 and the delocalization of Kir4.1. Dexamethasone seems to protect retina from these molecular changes by upregulating HSF1.
    • Accession Number:
      0 (Anti-Inflammatory Agents)
      0 (Aquaporin 4)
      0 (DNA-Binding Proteins)
      0 (Dystrophin)
      0 (Heat Shock Transcription Factors)
      0 (Hsf1 protein, mouse)
      0 (Kcnj10 (channel))
      0 (Potassium Channels, Inwardly Rectifying)
      0 (Transcription Factors)
      0 (apo-dystrophin 1)
      7S5I7G3JQL (Dexamethasone)
    • Publication Date:
      Date Created: 20170205 Date Completed: 20170621 Latest Revision: 20180102
    • Publication Date:
      20231215
    • Accession Number:
      10.1167/iovs.16-20617
    • Accession Number:
      28159978