TY - JOUR T1 - Effect of systemic treatment with Tauroursodeoxycholic Acid (TUDCA) on retinal ganglion cell death following optic nerve crush JF - bioRxiv DO - 10.1101/733568 SP - 733568 AU - Ying Li AU - Xian Zhang AU - Jiaxing Wang AU - Jana T. Sellers AU - Amber P. Boyd AU - John M. Nickerson AU - Jeffrey H. Boatright Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/13/733568.abstract N2 - The aim of this study was to investigate the protective effects of systemically administered tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model. TUDCA 500mg/kg was intraperitoneally (i.p.) injected into adult C57BL/6 mice three times per week. Two weeks after TUDCA treatment (6 injections), unilateral optic nerve crush was conducted followed by TUDCA treatment at the same day. The TUDCA treatment was continued until 1 week and 2 weeks after ONC. A control cohort was identically treated with drug vehicle (phosphate-buffered saline; PBS). Retinas were harvested for whole mount immunofluorescence staining with RGC markers and imaged by fluorescent confocal microscopy at 40x magnification. Fluorescing cells were counted by computer-assisted automated identification and counting software (CellProfiler). Cohort sampling sizes were N=4 and statistical tesing was by the Wilcoxon-Mann-Whitney Test. Significant loss (80%~85%) occurred in the PBS-injected group 1 and 2 weeks after ONC. One week after ONC, immunofluorescencing cell counts were 100±4.5 cells/per field in the PBS-injected control group and 177±19 cells/per field in the TUDCA-injected group according to Brn3a labeling (P<0.05). Two weeks after ONC, there also were more cells labeled by RGC pan-marker RBPMS in the TUDCA-injected group (158±12 cells/per field) than in the PBS-injected control group (97±1.8 cells/per field) (P<0.05). Delivery of TUDCA by i.p. injection increased survival of RGCs after ONC. These data suggest that it is worthwhile to further explore possible protective effects of TUDCA on RGC subtypes with regards to structure and function and in additional disease models that involve RGC loss. ER -