Elevated TGF beta signaling inhibits ocular vascular development

Alterations in the ocular vasculature are associated with retinal diseases such as retinopathy of prematurity and diabetic retinopathy. Vascular endot helial growth factor (VEGF) as a potent stimulator for normal and abnormal vascular growth has been extensively studied. However, little is known abou t secreted factors that negatively regulate vascular growth in ocular tissu es. We now report that expression of a self-activating TGF beta1 in the ocu lar lens of transgenic mice results in inhibition of retinal angiogenesis f ollowed by retinal degeneration. Transgenic TGF beta1 can rescue the hyperp lasic hyaloid tissue and reverse the corneal deficiency in TGF beta2-null e mbryos. These results demonstrate that TGF beta signaling modulates develop ment of ocular vasculature and cornea in a dosage-dependent manner and that TGF beta1 can substitute for TGF beta2 in ocular tissues. (C) 2001 Academi c Press.