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Fas ligand (CD95 ligand) controls angiogenesis beneath the retina

Nature Medicine volume 5, pages 292–297 (1999)Cite this article

Abstract

A principal cause of blindness is subretinal neovascularization associated with age-related macular degeneration. Excised neovascular membranes from patients with age-related macular degeneration demonstrated a pattern of Fas+ new vessels in the center of the vascular complex, surrounded by FasL+ retinal pigment epithelial cells. In a murine model, Fas (CD95)-deficient (lpr) and FasL-defective (gld) mice had a significantly increased incidence of neovascularization compared with normal mice. Furthermore, in gld mice there is massive subretinal neovascularization with uncontrolled growth of vessels. We found that cultured choroidal endothelial cells were induced to undergo apoptosis by retinal pigment epithelial cells through a Fas–FasL interaction. In addition, antibody against Fas prevented vascular tube formation of choroidal endothelial cells derived from the eye in a three-dimensional in vitro assay. Thus, FasL expressed on retinal pigment epithelial cells may control the growth and development of new subretinal vessels that can damage vision.

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Figure 1: Subretinal neovascularization in age-related macular degeneration.
Figure 2: Incidence and area of laser-induced subretinal neovascular complexes.
Figure 3: Subretinal neovascularization in bone marrow chimeras.
Figure 4: Sensitivity of HCEC to Fas-mediated death.

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Acknowledgements

This work is supported by National Eye Institute grants EY06765 and EY08972 (T.A.F.), The Foundation for Fighting Blindness, Hunt Valley, Maryland (H.J.K.) and a Department of Ophthalmology and Visual Sciences grant from Research to Prevent Blindness, New York, New York. M.A.L. was supported by a Research to Prevent Blindness Medical Student Eye Research Fellowship.

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  1. Department of Ophthalmology and Visual Sciences, Department of Pathology, Washington University School of Medicine, St. Louis, 63110, Missouri, USA

    Henry J. Kaplan, Marc A. Leibole, Tongalp Tezel & Thomas A. Ferguson

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Correspondence to Thomas A. Ferguson.

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Kaplan, H., Leibole, M., Tezel, T. et al. Fas ligand (CD95 ligand) controls angiogenesis beneath the retina. Nat Med 5, 292–297 (1999). https://doi.org/10.1038/6509

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