Taurocholic acid inhibits features of age-related macular degeneration in vitro. (April 2020)

• Record Type: Journal Article
• Authors: Warden, Cassandra; Barnett, Joshua M.; Brantley, Milam A.
• Is Part Of: Experimental eye research. Volume 193(2020)
• Publication Date: 2020-04
• Subjects: Age-related macular degeneration -- Bile acids -- Taurocholic acid -- Retinal pigment epithelium -- Choroidal endothelial cells; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.107974
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Previous metabolomics studies from our lab found altered plasma levels of bile acids in patients with age-related macular degeneration (AMD) compared to controls. In this study, we investigated the ability of the bile acid taurocholic acid (TCA) to inhibit features of AMD modeled in vitro . Paraquat was used to induce oxidative stress in HRPEpiC primary retinal pigment epithelial (RPE) cells. Cells were treated with 300 μM paraquat alone or with TCA (10, 50, 100, 200, or 500 μM). RPE tight junction integrity was assessed via ZO-1 immunofluorescence and transepithelial electrical resistance (TEER) measurements. RF/6A macaque choroidal endothelial cells were treated with 100 ng/mL vascular endothelial growth factor (VEGF) to induce angiogenesis. The effect of TCA on VEGF-induced angiogenesis was evaluated with cell proliferation, cell migration, and tube formation assays. Addition of TCA at 100 ( P = 8.6 × 10 −4 ), 200 ( P = 0.0035), and 500 ( P = 2.1 × 10 −4 ) μM resulted in significant preservation of TEER in paraquat treated cells. In RF/6A cells, TCA did not significantly affect VEGF-induced cell proliferation. VEGF-induced migration of RF/6A cells was significantly inhibited at TCA concentrations of 100 ( P = 0.010), 200 ( P = 0.023) and 500 ( P = 0.0049) μM. VEGF-induced tube formation was significantly inhibited when treated with 200 ( P = 0.014) and 500 ( P = 7.1 × 10 −4 ) μM TCA. In vitro, TCA promoted RPE cell integrity and diminished VEGF-induced choroidal endothelial cell migration and tube formation. This suggests that TCA may have protective effects against both degenerative and neovascular AMD. Highlights: TCA protects RPE monolayer tight junctions in vitro . TCA inhibits VEGF-induced cell migration in choroidal endothelial cells in vitro . TCA inhibits VEGF-induced tube formation in choroidal endothelial cells in vitro .