title: Altered astrocyte morphology and vascular development in dystrophin-Dp71-null mice.
abstract: Understanding retinal vascular development is crucial because many retinal vascular diseases such as diabetic retinopathy (in adults) or retinopathy of prematurity (in children) are among the leading causes of blindness. Given the localization of the protein Dp71 around the retinal vessels in adult mice and its role in maintaining retinal homeostasis, the aim of this study was to determine if Dp71 was involved in astrocyte and vascular development regulation. An experimental study in mouse retinas was conducted. Using a dual immunolabeling with antibodies to Dp71 and anti-GFAP for astrocytes on retinal sections and isolated astrocytes, it was found that Dp71 was expressed in wild-type (WT) mouse astrocytes from early developmental stages to adult stage. In Dp71-null mice, a reduction in GFAP-immunopositive astrocytes was observed as early as postnatal day 6 (P6) compared with WT mice. Using real-time PCR, it was showed that Dp71 mRNA was stable between P1 and P6, in parallel with post-natal vascular development. Regarding morphology in Dp71-null and WT mice, a significant decrease in overall astrocyte process number in Dp71-null retinas at P6 to adult age was found. Using fluorescence-conjugated isolectin Griffonia simplicifolia on whole mount retinas, subsequent delay of developing vascular network at the same age in Dp71-null mice was found. An evidence that the Dystrophin Dp71, a membrane-associated cytoskeletal protein and one of the smaller Duchenne muscular dystrophy gene products, regulates astrocyte morphology and density and is associated with subsequent normal blood vessel development was provided.
authors.affiliation: Ophthalmology Department, Avicenne Hospital, 125 Rue De Stalingrad, Bobigny, France.|Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Giocanti-Auregan
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Vacca
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Bénard
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Sijia
authors.initials: S
authors.lastname: Cao
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Siqueiros
authors.affiliation: Department of Genetics & Molecular Biology, Research Centre for Advanced Studies, IPN, Av. I.P.N. 2508, Mexico City, C.P., 07360, Mexico.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Montañez
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.|Centre Hospitalier National D'ophtalmologie Des Quinze-Vingts, DHU View Maintain, INSERM-DHOS CIC 1423, Paris, F-75012, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Paques
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.|Centre Hospitalier National D'ophtalmologie Des Quinze-Vingts, DHU View Maintain, INSERM-DHOS CIC 1423, Paris, F-75012, France.|Fondation Ophtalmologique Rothschild, Paris, F-75019, France.
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Guillonneau
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rendon
authors.affiliation: Institut De La Vision, Sorbonne Universités, UPMC Univ Paris 06, UMR_S, 968, Paris, F-75012, France.|INSERM, U_968, Paris, F-75012, France.|CNRS, UMR_7210, Paris, F-75012, France.|Ophthalmology Department, Hôpital Lariboisière, AP-HP, University Paris 7, Sorbonne Paris Cité, 2 Rue Ambroise Paré, Paris, 75010, France.
authors.forename: Ramin
authors.initials: R
authors.lastname: Tadayoni
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger; D012160:Retina / Q000166:cytology*; D012171:Retinal Vessels / Q000033:anatomy & histology* / Q000378:metabolism; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D005904:Glial Fibrillary Acidic Protein; C083970:R-cadherin; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C085339:apo-dystrophin 1; C528900:glial fibrillary astrocytic protein, mouse
keywords: angiogenesis; astrocytes; dystrophin Dp71; retinal vascular development