Purchase this article with an account.
Menaka Thounaojam, Shubhra Rajpurohit, Ravirajsinh Jadeja, Diana Gutsaeva, Pamela M Martin, Manuela Bartoli; Differential effects of bile acids on retinal barrier function in a mouse model of oxygen induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5417.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Emerging evidence suggests that secondary conjugated bile acids (BAs), such as ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) exert neurovascular protective effects in a number of retinal diseases. As part of their protective function, bile acids are suggested to stabilize barrier function, the direct effects of various secondary conjugated and unconjugated BAs on retinal barrier function has not been investigated. Herein, we studied the effects of different BAs on barrier function of human retinal endothelial cells (HuREC) and in a mouse model of oxygen induced retinopathy (OIR).
HuREC were treated with different concentration of VEGF (50-200) ng/ml and/or different doses (10-500 µM) of UDCA, TUDCA and glycoursodeoxycholic acid (GUDCA) for different times. Endothelial barrier function was evaluated by fluorescein isothiocyanate (FITC)-dextran permeability assay. In vivo studies were performed using the mouse model of retinopathy (OIR). The mice were treated with 50 mg/kg (i.p.) UDCA from days P7-P17. Isolectin B4 staining on flat mounted retinal preparations was performed at P17 to evaluate retinal vessel growth and distribution. The permeability of retinal vessels was assessed by Evans blue dye (EB) leakage assay. Further, these results were confirmed by evaluating changes in expression of tight junction proteins (ZO-1, occludin and claudin) by standard immunofluorescence and western blot techniques.
Treatment of HuREC with 20 ng/ml VEGF significantly induced time dependent cell barrier disruption. UDCA and TUDCA dose-dependently preserve barrier integrity in HuREC, whereas GUDCA had no effects. These observations were supported by changes in expression of various tight junction protein markers. Further, in vivo evans blue assay revealed less diffuse dye leakage in UDCA treated retinas and prevented loss of ZO-1 expression in retinas of OIR mice. No significant differences were noted in Claudin-1 expression between OIR and UDCA treated groups
In summary, herein we have found that secondary conjugated BAs possess differential ability to influence retinal vasculature barrier function with UDCA demonstrating stronger effects in vitro and in vivo. Our data suggest UDCA potential therapeutic application in retinal ischemic disorders involving blood retinal barrier breakdown.
This is a 2020 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only