Purchase this article with an account.
J.D. Ash, D.R. Graham; Inhibition of Retinal Vasculogenesis and Angiogenesis by Leukemia Inhibitory Factor (Lif) Requires Signaling in Vascular Endothelial Cells and Precursor Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1832.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Lens–specific expression of the LIF dramatically inhibited differentiation of the retina, and inhibited retinal vascularization. The inhibition was specific to the neural retina since LIF did not inhibit angiogenesis in the vitreous. It was possible that the primary affect was on the neural retina or on the vasculature. The purpose of this study was to determine weather or not LIF stimulation of receptors in vascular cells or the neural retinal was responsible for inhibiting retinal vascularization.
Transgenic Tie2–cre mice were used to inactivate the LIF receptor gp130 in vascular endothelial cells and vascular precursor cells. These mice were mated to transgenic mice expressing LIF in the ocular lens. We compared the LIF mediated inhibition of retinal vascularization in mice with functional gp130 to mice in which gp130 was inactivated by Tie2–cre only in vascular cells.
LIF stimulation inhibited all retinal vascularization as reported previously. This was observed in mice lacking cre and in mice that do not have the floxed allele of gp130. LIF stimulation did not inhibit retinal vascularization in mice with tissue specific inactivation of gp130.
Tissue specific inactivation of gp130 in vascular endothelial cells and precursors largely eliminated the ability of LIF to inhibit retinal vasculogenesis or angiogenesis. These results demonstrate that IL6 family of cytokines disrupt retinal vasculature by acting on receptors in vascular endothelial cells or their precursors and not by acting on receptor in glia or neurons.
This PDF is available to Subscribers Only