The role of macrophage migration inhibitory factor in physiological angiogenesis

Question: Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine. Recent studies suggest a role for MIF as an angiogenic factor activating and recruiting endothelial cells. The mouse retina is a well established model to study physiological angiogenesis. However, no studies have been performed yet aiming at the role of MIF. We investigate the role of MIF in the development of the retinal vasculature in the mouse.

Methods: MIF-knockout mice and C57BL/6 mice as wildtype (WT) were used. Retinal whole-mount immunofluorescence stainings for lectin and collagen IV were performed to analyze the superficial vascular layer at postnatal day 5 (P5) and the deep vascular layer at postnatal day 10 (P10). At P5, vessel outgrowth, capillary density, branchpoints and sprouting tips were quantified. At P10 we measured the total deep capillary area and the number of branchpoints.

Results: For the development of superficial vascular layer, there were no significant differences in any parameter between WT and MIF-knockout groups. For the development of deep vascular layer, the total deep capillary area was reduced in MIF-knockout mice without significance and the average number of branchpoints was decreased by 11.5% (P < 0.05) compared to WT controls.

Conclusion: Our study suggests that MIF has a modest effect on the development of the retinal deep capillary layer.