Effect of systemic treatment with Tauroursodeoxycholic Acid (TUDCA) on retinal ganglion cell death following optic nerve crush

Abstract

The aim of this study was to investigate the protective effects of systemically administered N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3- carboxamide (HIOC) or tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model. HIOC (50 mg/kg) or TUDCA (500mg/kg) were intraperitoneally (i.p.) injected into adult C57BL/6 mice three times per week. Two weeks after treatment (6 injections), unilateral optic nerve crush was conducted followed by treatment at the same day. The treatment was continued until 1 week or 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. This loss was partially but significantly prevented in drug-treated cohorts (P < 0.05). Delivery of HIOC or TUDCA by i.p. injection increased survival of RGCs after ONC. Protection was similar between treatment with either drug. These data suggest that it is worthwhile to further explore possible protective effects of HIOC or TUDCA on RGC subtypes with regards to structure and function and in additional disease models that involve RGC loss.