Objective: Define a role for perivascular cells during developmental retinal angiogenesis in the context of endothelial cell Notch1-DLL4 signaling at the multicellular network level.
Methods: The retinal vasculature is highly sensitive to growth factor mediated intercellular signaling. Although endothelial cell signaling has been explored in detail, it remains unclear how pericytes function to modulate these signals that lead to a diverse set of vascular network patterns in health and disease. We have developed an agent-based model of retinal angiogenesis that incorporates both endothelial cells and pericytes to investigate the formation of vascular network patterns as a function of pericyte coverage. We use our model to test the hypothesis that pericytes modulate Notch1-DLL4 signaling in endothelial cell-endothelial cell interactions.
Results: ABM simulations that include pericytes more accurately predict experimentally observed vascular network morphologies than simulations that lack pericytes, suggesting that pericytes may influence sprouting behaviors through physical blockade of endothelial intercellular connections.
Conclusion: This study supports a role for pericytes as a physical buffer to signal propagation during vascular network formation – a barrier that may be important for generating healthy microvascular network patterns.