Anti-angiogenic effect of TGFβ in aqueous humor

Neovascularization is mediated by various factors in ocular tissues. Recent studies have emphasized the role of vascular endothelial growth factor in the induction of angiogenesis. We have previously reported that aqueous humor (AH) suppressed vascular endothelial cell growth and angiogenesis. We speculated that the anti-angiogenic effect of AH is mediated by transforming growth factor beta (TGF beta). In order to clarify the presence of TGF beta in bovine AH, we applied it on the heparin-sepharose affinity column and prepared two fractions (bound and unbound fractions). We measured TGF beta concentration in each fraction and examined how the anti-TGF beta antibody decreased the inhibitory effect of AH on human umbilical vein endothelial cell. growth and on in vitro angiogenesis. We found the presence of TGF beta 2, but not TGF beta 1, in the heparin bound fraction, and the inhibitory effect was detected in the heparin-bound fraction. Anti-TGF beta antibody completely and dosed-dependently extinguished the inhibitory effect of AH. We propose that the inhibitory effect of AH on endothelial cell growth and in vitro angiogenesis are both mediated by TGF beta 2. Our results indicate TGF beta 2 is normally present in AH and protects the eye tissue against abnormal neovascularization.