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Brahim El Mathari, Hugo Charles-Messance, Claudine Grepin, Michel J Roux, Jose Alain Sahel, Ramin Tadayoni, Alvaro Rendon; Dystrophin-Dp71-null mouse presents retinal vascular inflammation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5819.
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© ARVO (1962-2015); The Authors (2016-present)
Dystrophin Dp71 is a cytoskeleton membrane associated protein, which is expressed in Müller cells and astrocytes. These two cell types contact and ensheath the retinal vascular plexus. The perivascular localization of Dp71 protein is fundamental for blood-retinal barrier (BRB) stabilization. Indeed, we have shown that the deletion of Dp71 induces a highly permeable BRB (Sene, 2009). Given that BRB breakdown is involved in retinal inflammation, here we undertook to investigate if the absence of Dp71 brings out retinal vascular inflammation?
The expression of VEGFa, ICAM-1 and CD11b was quantified by qPCR, ELISA and immunohistochemistry methods. Retinal leukostasis in mice was assessed after perfusion with FITC-conjugated concanavalin A.
VEGFa is overexpressed in DR and binds to VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFa mRNA and protein were overexpressed in the retina of KoDp71 mice compared to the wildtype. VEGFR-1 was also overexpressed. ICAM-1 is expressed on endothelial cells surface to recruits leukocytes. CD11b is expressed on the surface of leukocytes to bind ICAM-1. The expression of ICAM-1 and CD11b was increased in absence of Dp71 protein. Leukostasis which is a hallmark of inflammation was increased in KoDp71 mice.
The deletion of Dp71 protein induces retinal inflammation with overexpression of VEGFa, ICAM-1 and CD11b, leukostasis and breakdown of the blood-retinal barrier which are characteristic of retinal inflammation. All together these results suggest that the Dp71-null mouse could be a good model to study retinal vascular diseases like diabetic retinopathy.
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