Elevated TGFbeta signaling inhibits ocular vascular development.
Alterations in the ocular vasculature are associated with retinal diseases such as retinopathy of prematurity and diabetic retinopathy. Vascular endothelial growth factor (VEGF) as a potent stimulator for normal and abnormal vascular growth has been extensively studied. However, little is known about secreted factors that negatively regulate vascular growth in ocular tissues. We now report that expression of a self-activating TGFbeta1 in the ocular lens of transgenic mice results in inhibition of retinal angiogenesis followed by retinal degeneration. Transgenic TGFbeta1 can rescue the hyperplasic hyaloid tissue and reverse the corneal deficiency in TGFbeta2-null embryos. These results demonstrate that TGFbeta signaling modulates development of ocular vasculature and cornea in a dosage-dependent manner and that TGFbeta1 can substitute for TGFbeta2 in ocular tissues.
Zhao
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S
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. szhao@lexgen.com
Overbeek
P A
PA
D000818:Animals; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics; D005123:Eye / Q000098:blood supply*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D012162:Retinal Degeneration / Q000209:etiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor