Ursodeoxycholic Acid and Tauroursodeoxycholic Acid Suppress Choroidal Neovascularization in a Laser-Treated Rat Model

Purpose: The aim of this study was to investigate the suppressing effects of systemically administered ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) on choroidal neovascularization (CNV) in a laser-treated rat model. Methods: CNV was induced by argon laser photocoagulation in the right eye of each animal. UDCA 500 mg/kg, TUDCA 100 mg/kg, or vehicle was intraperitoneally injected at 24 h before and daily after laser treatment. Fourteen days after laser treatment, fluorescein angiography was performed to evaluate leakage from CNV and eyes were enucleated for histologic evaluation. Vascular endothelial growth factor (VEGF) levels in the retina were measured using enzyme-linked immunosorbent assay at 3 days after laser treatment and were compared between the UDCA, TUDCA, and control groups. Results: The proportion of CNV lesions showing clinically significant fluorescein leakage was lower in the UDCA and TUDCA groups (42%, P = 0.0124; and 46%, P = 0.0292) than in the control group (67%). CNV lesion dimensions including CNV area and CNV/choroid thickness ratio were also significantly reduced in the UDCA and TUDCA groups (7,664 +/- 630 mu m(2), P < 0.001 and 8,558 +/- 570 mu m(2), P < 0.001; 2.35 +/- 0.16, P = 0.026 and 2.27 +/- 0.15, P = 0.003) compared with the control group (12,147 +/- 661 mu m(2) and 3.10 +/- 0.27). The VEGF level in the retina after laser treatment was lower in the TUDCA group than that in the control group (9.0 +/- 2.7 pg/mg vs. 29.4 +/- 8.2 pg/mg, P = 0.032), whereas the UDCA group showed no difference. Conclusions: The systemic administration of UDCA and TUDCA suppressed laser-induced CNV formation in rats, which might be associated with anti-inflammatory action. The result indicates that UDCA and TUDCA are potential candidate drugs for the treatment of many CNV-related retinal diseases, including age-related macular degeneration.