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Menaka Thounaojam, Diana Gutsaeva, Folami Lamoke Powell, Pamela M Martin, Manuela Bartoli, Ravirajsinh Jadeja; Differential anti-angiogenic properties of the bile acids UDCA and TUDCA in human retinal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5486. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Emerging evidence suggest that secondary conjugated bile acids, such as ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA), possess neuroprotective and vasculoprotective properties and may exert beneficial effects in a number of retinal diseases. However, the direct activity of UDCA and TUDCA on retinal microvascular endothelial cell (HuREC) has not been investigated. Here, we have investigate the effects of UDCA and TUDCA on barrier function and VEGF induced migration and angiogenesis in HuREC.
HuREC were treated with 20 ng/ml of VEGF and/or different doses (10-500 µM) of TUDCA or UDCA for different times. Endothelial barrier function was evaluated by fluorescein isothiocyanate (FITC)-dextran permeability assay. The angiogenic potential was evaluated using tube formation and cell sprouting assays. Scratch assay was performed to assess endothelial cell migration. Cytotoxicity of TUDCA and UDCA were evaluated using MTT cell viability assay.
Treatment of HuREC with 20 ng/ml VEGF significantly induced time dependent cell migration, tube formation and sprouting. UCDA dose-dependently halted VEGF-induced migration, tube formation and sprouting. UCDA inhibitory effects towards VEGF-promoted angiogenesis peaked at 100µM. Interestingly, TUCDA did not prevent any of these VEGF-related effects on HuREC. Further, UDCA halted VEGF-induced HuREC permeability, whereas TUCDA had no effects. Cytotoxicity assay indicated that both bile acids had no adverse effects on survival of HuREC. Hence, the observed anti-angiogenic potential of UDCA is not due to its cytotoxic effects.
In summary, here we have shown that UCDA and TUCDA possess differential ability to modulate VEGF-mediated angiogenesis effects on HuREC. The results of our studies will help to better characterize the specificity of the therapeutic action of these compounds for the treatment of ischemic retinopathies.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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