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



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.



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.



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.
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France 2Department of Genetics & Molecular Biology, Research Centre for Advanced Studies, Instituto Politécnico Nacional, Mexico City, Mexico.
Lourdes
L
Siqueiros-Marquez
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France.
Romain
R
Bénard
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France.
Ophélie
O
Vacca
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France.
Hugo
H
Charles-Messance
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France.
Rodrigo
R
Bolaños-Jimenez
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France.
Xavier
X
Guilloneau
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France.
Florian
F
Sennlaub
Department of Genetics & Molecular Biology, Research Centre for Advanced Studies, Instituto Politécnico Nacional, Mexico City, Mexico.
Cecilia
C
Montañez
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France 3Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Département Hospitalo-Universitaire (DHU) Sight Restore, INSERM-Direction de l'Hospitalisation et de la Direction des Soins Centre d'Investigation Clinique, Paris, France 4Fondation Ophtalmologique Adolphe de Rothschild, Département Hospitalo-Universitaire (DHU) Sight Restore, Paris, France.
José Alain
JA
Sahel
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France.
Alvaro
A
Rendon
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France 5Ophthalmology Department, Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris (AP-HP), University Paris 7, DHU Vision and Handicaps-Sorbonne Paris Cité, Paris, France.
Ramin
R
Tadayoni
Sorbonne Universités, Pierre et Marie Curie University, University Paris 06, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique Institut de la Vision, Paris, France 6Ophthalmology Department, Avicenne Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), University Paris 13, DHU Vision and Handicaps, Bobigny, France.
Audrey
A
Giocanti-Aurégan
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051401:Aquaporin 4 / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D016189:Dystrophin / Q000378:metabolism; D063928:Ependymoglial Cells / Q000187:drug effects* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000098854:Kcnj10 Channel
D000893:Anti-Inflammatory Agents; D051401:Aquaporin 4; D004268:DNA-Binding Proteins; D016189:Dystrophin; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D014157:Transcription Factors; C085339:apo-dystrophin 1; D003907:Dexamethasone