Protective effects of different bile acids against pathological neovascularization

Abstract

Emerging evidence suggest that the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine (TUDCA) conjugates, possess neuroprotective and vasculoprotective properties and may exert beneficial effects in a number of neovascular diseases including ischemic retinopathy such as retinopathy of prematurity (ROP). However, the direct activity of UDCA or TUDCA in the treatment of retinal neovascularization has not been previously investigated. Herein, we studied the effects of different bile acids on in vitro angiogenesis in human retinal endothelial cells (HuREC) and retinal vascularization in vivo using the mouse model of oxygen induced retinopathy (OIR), an experimental model of ROP. HuREC were treated with 20 ng/ml of VEGF and/or different doses (10–500 μM) of UDCA or TUDCA for different times. Angiogenic responses were evaluated using tube formation assay. Treatment of HuREC with VEGF significantly induced time dependent tube formation. UDCA dose‐dependently halted VEGF‐induced tube formation, whereas TUDCA had no effect. For the in vivo studies, mice were subjected to OIR and treated with UDCA and TUDCA (administered i.p.) from days P12–P17 (the neovascular stages). Isolectin B4 staining on flat mounted retinal preparations was performed at P17 to evaluate retinal vessel growth and distribution. The results of this analysis revealed that UDCA in the OIR mice halted pathological neovascularization, but did not alter normal vascularization. On the contrary, treatment of the mice with TUDCA failed to block retinal neovascularization, thus confirming the in vitro data. In summary, here we have shown that the bile acids UCDA and TUCDA possess differential ability to modulate VEGF‐mediated angiogenesis effects on HuREC and on retinal pathological neovascularization in vivo. The results of studies support the hypothesis that UDCA could be a potential therapeutic option for ROP as it exerts protection even by systemic administration and does not alter normal progression of vessel formation.Support or Funding InformationThis study is supported by R03HD097660‐01.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.