Tool from ancient pharmacopoeia prevents vision loss

[摘要] Purpose: Bear bile has been used in Asia for over 3,000 years totreat visual disorders, yet its therapeutic potential remains unexploredin Western vision research. The purpose of this study was to testwhether treatment of mice undergoing retinal degeneration withtauroursodeoxycholic acid (TUDCA), a primary constituent of bear bile,alters the course of degeneration.Methods: Two retinal degeneration models were tested: the rd10mouse, which has a point mutation in the gene encoding the beta subunitof rod phosphodiesterase, and light induced retinal damage (LIRD). ForLIRD studies, albino Balb/C adult mice were subcutaneously injected withTUDCA (500 mg/kg body weight) or vehicle (0.15 M NaHCO3). Sixteen hlater, each mouse received repeat injections. Half of each treatmentgroup was then placed in bright light (10,000 lux) or dim light (200lux) for seven h. At the end of exposure, animals were transferred totheir regular housing. Electroretinograms (ERGs) were assessed 24 hlater, mice sacrificed, eyes embedded in paraffin and sectioned, andretina sections assayed for morphology and apoptosis by TUNEL andanti-active caspase-3 immunoreactivity via fluorescent confocalmicroscopy. A subset of mice were sacrificed 8 and 15 days afterexposure and retina sections analyzed for morphology and apoptosis. Forrd10 studies, mice were injected subcutaneously with TUDCA orvehicle at postnatal (P) days 6, 9, 12, and 15. At p18, ERGs wererecorded, mice were euthanized and eyes were harvested, fixed, andprocessed. Retinal sections were stained (toluidine blue), and retinalcell layers morphometrically analyzed by light microscopy. Consecutivesections were analyzed for apopotosis as above.Results: By every measure, TUDCA greatly slowed retinal degenerationin LIRD and rd10 mice. ERG a-wave and b-wave amplitudes were greaterin mice treated with TUDCA compared to those treated with vehicle.Retinas of TUDCA-treated mice had thicker outer nuclear layers, morephotoreceptor cells, and more fully-developed photoreceptor outersegments. Finally, TUDCA treatments dramatically suppressed signs ofapoptosis in both models.Conclusions: Systemic injection of TUDCA, a primary constituent ofbear bile, profoundly suppressed apoptosis and preserved function andmorphology of photoreceptor cells in two disparate mouse models ofretinal degeneration. It may be that bear bile has endured so long inAsian pharmacopeias due to efficacy resulting from this anti-apoptoticand neuroprotective activity of TUDCA. These results also indicate thata systematic, clinical assessment of TUDCA may be warranted.

[学科分类] 生物化学/生物物理