Macrophages have a critical function in the recognition and engulfment of dead cells. In some settings, macrophages also actively signal programmed cell death. Here we show that during developmentally scheduled vascular regression, resident macrophages are an obligatory participant in a signaling switch that favors death over survival. This switch occurs when the signaling ligand angiopoietin 2 has the dual effect of suppressing survival signaling in vascular endothelial cells (VECs) and stimulating Wnt ligand production by macrophages. In response to the Wnt ligand, VECs enter the cell cycle and in the absence of survival signals, die from G1 phase of the cell cycle. We propose that this mechanism represents an adaptation to ensure that the macrophage and its disposal capability are on hand when cell death occurs.

modulates VEGF-A-mediated Akt signaling and capillary survival in the developing retina.

No abstract

Purpose: It has still not been determined whether the retinal mechanism causing form-deprivation myopia (FDM) is different from that causing lens-induced myopia (LIM). We previously reported that FDM was blocked by an intravitreal injection of the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). In this study, we investigated the effect of L-NAME on LIM in chicks. Method: The left eyes of 6-day-old chicks were injected with 30 µl of nontoxic concentrations of L-NAME (≤360 mM) or saline. The right eyes were injected with 30 µl of saline. A –16 dpt lens was placed in front of the left eye for 6 days. Another group of 6 chicks were injected with 180 mML-NAME (left eye) and with saline (right eye) before placing –16 dpt lenses in front of both eyes. After removing the lens, the refraction and the axial length were measured. The effect of L-NAME (180 mM) on the retina of a separate group of chicks was examined by electroretinography 60 min after an intravitreal injection in non-LIM-treated eyes. Results: The eyes of chicks that were injected with 180 or 360 mML-NAME were less myopic and had significantly shorter axial lengths than control eyes. A significant decrease of the On response and an increase of the Off response were observed. Conclusion: The injection of L-NAME into developing chick eyes that were then covered with a –16 dpt lens resulted in a modifications of retinal function and an inhibition of the development of myopia. These results, combined with the earlier findings, suggest that NO modulates a common retinal pathway that leads to both LIM and FDM.