Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy
Science. 2020 Aug 21;369(6506):eaay5356. doi: 10.1126/science.aay5356
François Binet, Gael Cagnone, Sergio Crespo-Garcia, Masayuki Hata, Mathieu Neault, Agnieszka Dejda, Ariel M Wilson, Manuel Buscarlet, Gaelle Tagne Mawambo, Joel P Howard, Roberto Diaz-Marin, Celia Parinot, Vera Guber, Frédérique Pilon, Rachel Juneau, Rémi Laflamme, Christina Sawchyn , Karine Boulay, Severine Leclerc, Afnan Abu-Thuraia, Jean-François Côté, Gregor Andelfinger, Flavio A Rezende, Florian Sennlaub, Jean-Sébastien Joyal, Frédérick A Mallette, Przemyslaw Sapieha
In developed countries, the leading causes of blindness, such as diabetic retinopathy, are characterized by disorganized vasculature that can become fibrotic. Although many such diseased vessels often regress naturally and avoid sight-threatening complications, the underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative diabetic retinopathy and a mouse model of ischemic retinopathies to identify an unconventional role of neutrophils in vascular remodeling during advanced sterile inflammation. Senescent vasculature releases a secretome that attracts neutrophils and triggers the production of neutrophil extracellular traps (NETs). NETs eventually eliminate diseased endothelial cells and remodel diseased vessels. Genetic or pharmacological inhibition of NETosis prevents regression of senescent vessels and prolongation of disease. Thus, removal of senescent retinal blood vessels leads to reparative vascular remodeling.
