Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Biomolecules. 2021 Apr 23;11(5):626. doi: 10.3390/biom11050626.
We previously demonstrated that the bile acid taurocholic acid (TCA) inhibits features of age-related macular degeneration (AMD) in vitro. The purpose of this study was to determine if the glycine-conjugated bile acids glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and glycoursodeoxycholic acid (GUDCA) can protect retinal pigment epithelial (RPE) cells against oxidative damage and inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in choroidal endothelial cells (CECs). Paraquat was used to induce oxidative stress and disrupt tight junctions in HRPEpiC primary human RPE cells. Tight junctions were assessed via transepithelial electrical resistance and ZO-1 immunofluorescence. GCA and GUDCA protected RPE tight junctions against oxidative damage at concentrations of 100-500 µM, and GDCA protected tight junctions at 10-500 µM. Angiogenesis was induced with VEGF in RF/6A macaque CECs and evaluated with cell proliferation, cell migration, and tube formation assays. GCA inhibited VEGF-induced CEC migration at 50-500 µM and tube formation at 10-500 µM. GUDCA inhibited VEGF-induced CEC migration at 100-500 µM and tube formation at 50-500 µM. GDCA had no effect on VEGF-induced angiogenesis. None of the three bile acids significantly inhibited VEGF-induced CEC proliferation. These results suggest glycine-conjugated bile acids may be protective against both atrophic and neovascular AMD.
我们之前已经证明胆汁酸牛磺胆酸（TCA）可抑制体外年龄相关性黄斑变性（AMD）的特征。本研究的目的是确定甘氨酸结合胆汁酸甘氨胆酸（GCA）、甘脱氧胆酸（GDCA）和甘氨鹅脱氧胆酸（GUDCA）是否可以保护视网膜色素上皮（RPE）细胞免受氧化损伤，并抑制脉络膜内皮细胞（CEC）中血管内皮生长因子（VEGF）诱导的血管生成。百草枯用于诱导 HRPEpiC 原代人 RPE 细胞的氧化应激和破坏紧密连接。通过跨上皮电阻和 ZO-1 免疫荧光评估紧密连接。GCA 和 GUDCA 在 100-500 µM 浓度下保护 RPE 紧密连接免受氧化损伤，GDCA 在 10-500 µM 浓度下保护紧密连接。用 VEGF 在 RF/6A 猕猴 CEC 中诱导血管生成，并通过细胞增殖、细胞迁移和管形成测定进行评估。GCA 在 50-500 µM 时抑制 VEGF 诱导的 CEC 迁移，在 10-500 µM 时抑制管形成。GUDCA 在 100-500 µM 时抑制 VEGF 诱导的 CEC 迁移，在 50-500 µM 时抑制管形成。GDCA 对 VEGF 诱导的血管生成没有影响。三种胆汁酸均未显著抑制 VEGF 诱导的 CEC 增殖。这些结果表明甘氨酸结合胆汁酸可能对萎缩性和新生血管性 AMD 均具有保护作用。
