期刊
BIOMOLECULES
卷 11, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/biom11050626
关键词
age-related macular degeneration; bile acids; angiogenesis; RPE; choroidal endothelial cell; GCA; GDCA; GUDCA
资金
- National Institutes of Health [R01 EY022618, P30 EY008126]
- Edward N. & Della L. Thome Memorial Foundation Awards Program in Age-Related Macular Degeneration Research
- Research to Prevent Blindness
This study found that GCA, GDCA, and GUDCA can protect RPE cells against oxidative damage and inhibit VEGF-induced angiogenesis in CECs, suggesting they may be protective against both atrophic and neovascular AMD.
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 mu M, and GDCA protected tight junctions at 10-500 mu M. 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 mu M and tube formation at 10-500 mu M. GUDCA inhibited VEGF-induced CEC migration at 100-500 mu M and tube formation at 50-500 mu M. 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.
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