In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many such pathological vessels often naturally regress and spare 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 for neutrophils in vascular remodeling during late-stage sterile inflammation. Senescent vasculature released a secretome that attracted neutrophils and triggered the production of neutrophil extracellular traps (NETs). NETs ultimately cleared diseased endothelial cells and remodeled unhealthy vessels. Genetic or pharmacological inhibition of NETosis prevented the regression of senescent vessels and prolonged disease. Thus, clearance of senescent retinal blood vessels leads to reparative vascular remodeling.

Background:The MerTK receptor is necessary for retinal phagocytosis and its daily rhythm. Results: MerTK is cleaved from the apical cell surface in vitro and in vivo, reducing the phagocytic capacity of RPE cells. Conclusion: MerTK cleavage might help control the duration of the daily phagocytic peak. Significance: Our data show that extracellular cleavage of MerTK partly regulates retinal phagocytosis.