Retinal Pigmented Epithelium-Derived Ectopic Norrin Does Not Promote Intraretinal Angiogenesis in Transgenic Mice

Formation of intraretinal capillaries and inner blood-retinal barrier during development requires norrin, a ligand of the canonical wingless/integrated (Wnt)/β-catenin signaling pathway. Here we addressed the question whether retinal pigmented epithelium (RPE)-derived overexpression of norrin in transgenic mice rescues the vascular phenotype caused by norrin deficiency. To this end, we generated Ndp^KO/Rpe65-Norrin mice and analyzed the activation of β-catenin signaling, the development of intraretinal capillaries, and the expression of blood-retinal barrier marker molecules. RPE-derived norrin induced retinal β-catenin signaling but failed to rescue the vascular developmental defects and the breakdown of the blood-retinal barrier in norrin-deficient mice. Sites of ectopic norrin expression and the amounts of secreted transgenic protein are critical factors to enable the angiogenic properties of norrin.