Neuron-Derived Semaphorin 3A Is an Early Inducer of Vascular Permeability in Diabetic Retinopathy via Neuropilin-1

• DOI: 10.1016/j.cmet.2013.09.003
• Publication Date: 2013-10-01T15:46:07Z
• Authors: Agustin Cerani; Nicolas Tetreault; Catherine Menard; Eric Lapalme; Chintan Patel; Nicholas Sitaras; Felix Beaudoin; Dominique Leboeuf; Vincent De Guire; François Binet; Agnieszka Dejda; Flavio A. Rezende; Khalil Miloudi; Przemyslaw Sapieha
• Keywords: Vascular permeability

The deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation diabetic retinopathy (DR) clinical feature most closely associated with loss sight. We provide evidence from both human animal studies for critical role classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability retinas via its cognate receptor neuropilin-1. reveal that 3A induced early hyperglycemic phases diabetes within retina precipitates initial breakdown endothelial function. demonstrate, by series orthogonal approaches, neutralization efficiently prevents diabetes-induced retinal leakage stage disease when growth factor inefficient. These observations were corroborated TgCre-Esr1/Nrp1flox/flox conditional knockout mice. Our findings identify therapeutic target further neurovascular crosstalk pathogenesis DR.