title: Changes in aquaporin-4 and Kir4.1 expression in rats with inherited retinal dystrophy.
abstract: Muller glial cells (MGC) are essential for normal functioning of retina. They are especially involved in potassium (K+) and water homeostasis, via inwardly rectifying K+ (Kir 4.1) and aquaporin-4 (AQP4) channels respectively. Because MGC appear morphologically and functionally altered in most retinal pathologies, we studied the expression of AQP 4 and Kir 4.1 during the time course of progressive retinal degeneration in Royal College of Surgeons (RCS) rats, an animal model for the hereditary human retinal degenerative disease Retinitis pigmentosa. Simultaneous detection of AQP4 and Kir 4.1 was performed by quantitative real-time polymerase chain reaction (QRT-PCR), Western blot and immunohistochemistry at birth and during progression of the pathology. Although small quantities of AQP4 and Kir 4.1 mRNA were detected at birth (postnatal day (PNd) 0) in both control and dystrophic rat retinas, proteins could not be detected at this age. Detectable proteins appeared in the second week of postnatal life. From PNd15 onwards, the time course in the expression of both AQP4 and Kir 4.1 mRNAs and protein was similar in dystrophic and control rats, with a progressive increase peaking at PNd60 and a subsequent decrease by one year. AQP4 protein and mRNA content were significantly lowered in dystrophic compared to control rats. Kir 4.1 protein levels were also lower in dystrophic retinas, while mRNA concentrations were unchanged and/or slightly higher in dystrophic rats. The discrepancies between Kir4.1 mRNA and protein suggest perturbation in protein translation due to the pathology. AQP4 and Kir 4.1/vimentin co-immunolabeling showed that: 1) apical radial processes of some MGC invaded the subretinal zone, and 2) MGC morphology was distorted in advanced pathology. MGC became hypertrophic both during the pathology and also with age in control rats. In conclusion, our results confirm that this inherited photoreceptor degeneration also leads to progressive alterations in physiological and morphological parameters of MGC which may aggravate retinal impairment.
authors.affiliation: INSERM U1138 - Equipe 17: De la Physiopathologie des maladies rétiniennes aux Avancées Cliniques, Université Pierre et Marie Curie Paris VI, Université Paris-Descartes- Sorbonne, Paris Cité, Centre de Recherches des Cordeliers, 15, rue de l'Ecole de Médecine, 75006, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Lassiale
authors.affiliation: Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010, Paris, France; Fondation Ophtalmologique Adolphe de Rothschild, 25-29, rue Manin, 75019, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Valamanesh
authors.affiliation: INSERM U1138 - CICC, Université Paris-Descartes- Sorbonne, Paris Cité, Centre de Recherches des Cordeliers, Université Pierre et Marie Curie, Université Paris-Descartes, 15, rue de l'Ecole de Médecine, 75006, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.affiliation: CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, 5 rue Blaise Pascal, F-67084, Strasbourg, France.
authors.forename: D
authors.initials: D
authors.lastname: Hicks
authors.affiliation: INSERM U1138 - Equipe 17: De la Physiopathologie des maladies rétiniennes aux Avancées Cliniques, Université Pierre et Marie Curie Paris VI, Université Paris-Descartes- Sorbonne, Paris Cité, Centre de Recherches des Cordeliers, 15, rue de l'Ecole de Médecine, 75006, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Abitbol
authors.affiliation: INSERM U1138 - Equipe 17: De la Physiopathologie des maladies rétiniennes aux Avancées Cliniques, Université Pierre et Marie Curie Paris VI, Université Paris-Descartes- Sorbonne, Paris Cité, Centre de Recherches des Cordeliers, 15, rue de l'Ecole de Médecine, 75006, Paris, France; Université de Franche-Comté, Besancon, France. Electronic address: claudine.botteri@crc.jussieu.fr.
authors.forename: C
authors.initials: C
authors.lastname: Versaux-Botteri
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D009457:Neuroglia / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000473:pathology; D058499:Retinal Dystrophies / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D000098854:Kcnj10 Channel
chemical_list: D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D014746:Vimentin
keywords: AQP4; Kir 4.1; Muller cells; RCS rats; Retina; Vimentin