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Audrey Giocanti, Ophélie Vacca, Romain Benard, sijia Cao, Lourdes Siqueiros, Michel Paques, José-Alain Sahel, Florian Sennlaub, Xavier P Guillonneau, Alvaro Rendon, Ramin Tadayoni; Alteration of astrocyte and retinal vessel morphology in absence of Dystrophin Dp71. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4532. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Understanding retinal vascular development is important because many retinal vascular diseases such as diabetic retinopathy (in adults) or retinopathy of prematurity (in children) are among the leading causes of blindness. The protein Dp71 is located in Muller glial cells (MGC) around the retinal vessels in adult mice and participates to the maintenance of retinal homeostasis and blood retinal barrier. The aim of this study was to determine if Dp71was involved in astrocyte morphology and vascular development in mice.
We conducted an experimental study in mouse retinas. We labeled retinal sections and isolated astrocytes with antiH4 (pan specific antibody to all the Dystrophins) and antiGFAP antibodies. The localization of Dp71 was assessed par comparison between staining in wild type mice and Dp71-null mice. We evaluated at P3, P6 and P12 the area of retina covered by retinal vessels in both strains, using fluorescence-conjugated isolectin Griffonia simplicifolia. On retinal whole mounts, the same stainings were applied, and we quantified the astrocyte and vascular network morphologies.
We have first shown that Dp71 was expressed in retinal astrocytes. In Dp71-null mice, a reduction in GFAP-immunopositive astrocytes was observed as early as postnatal day 6 (P6) compared to WT mice. Regarding morphology in Dp71-null and WT mice, we found a significant decrease in overall process number in Dp71-null retinas at P6 to adult age. We also found subsequent delay of developing vascular network at the same age in Dp71-null mice associated with altered retinal vessel morphology.
We provide 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.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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