Involvement of fibroblast growth factors in choroidal angiogenesis and retinal vascularization.
Fibroblast growth factors such as FGF-2 are potent mitogens for endothelial cells and induce their assembly into vascular-like structures in culture and in in vivo assays. However, their putative functions during physiological vascularization are poorly documented. In this study, the eye was used as a model for analyzing the vascular defects caused by targeted FGF inhibition in transgenic mice. Choroidal and retinal vascularizations were studied by immunohistochemistry on whole-mount preparations. Soon after activation of the transgene, angiogenesis that normally occurs during the second half of gestation in the choroid was strongly inhibited resulting in poor capillary density and branching. Later retinas strikingly failed to develop a primary vascular plexus suggesting a defect in induction of vessel assembly. Hyaloid vessels that supply the retina during the fetal period did not regress at birth and later gave rise to unexpected massive neovascularization. This model illustrates major functions of FGFs at different early stages of physiological vascularization. Both the failure in hyaloid regression and the intense angiogenic invasion of endothelial cells into the retina may serve as a model for some related human ocular pathologies.
Rousseau
Benoît
B
Laboratoire des Mécanismes Moléculaires de l'Angiogenèse, INSERM EMI 01-13, Avenue des Facultés, Université de Bordeaux 1, 33405 Talence, France.
Larrieu-Lahargue
Frédéric
F
Bikfalvi
Andréas
A
Javerzat
Sophie
S
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002829:Choroid / Q000098:blood supply* / Q000196:embryology; D005346:Fibroblast Growth Factors / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors*; D012160:Retina / Q000166:cytology / Q000196:embryology*; D012171:Retinal Vessels / Q000196:embryology*
D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors