Abstract
Purpose: :
Tauroursodeoxycholic acid (TUDCA) is a naturally–occurring bile acid that is neuroprotective in models of neurodegenerative disease. We tested whether TUDCA similarly prevents light–induced photoreceptor apoptosis, retinal degeneration, and visual function loss.
Methods: :
Albino Balb/C adult mice previously maintained on a 12:12 light:dark cycle were subcutaneously injected with TUDCA (52 mg/kg body weight) or vehicle (0.15 M NaHCO3). Sixteen hours later, each mouse received repeat injections. Half of each treatment group was then placed in bright light (10,000 lux) or dim light (200 lux) for seven hours at a monitored temperature of 27+/–2 oC. At the end of exposure, animals were transferred to their regular housing with 12:12 room lighting. Repeat injections were given every three days. One day, one week, or two weeks later, ERGs were assessed, mice sacrificed, eyes embedded in paraffin and sectioned, and retina sections assayed for morphology and apoptosis by TUNEL and anti–active caspase–3 immunoreactivity via fluorescent confocal microscopy.
Results: :
For vehicle–treated mice, bright light exposure resulted in substantial TUNEL signal in photoreceptor cells, whereas no apoptosis was detected in dim light exposed retinas or in other retinal nuclear layers of any treatment group. TUDCA treatment prevented the appearance of TUNEL signal. Similarly, TUDCA treatment prevented the appearance of anti–activated caspase–3 immunoreactivity induced by bright light exposure. Bright light exposure caused photoreceptor cell loss, outer nuclear layer thinning, and outer segment layer thinning, responses that were prevented by TUDCA treatment. ERG analysis revealed that bright light exposure drastically reduced a– and b–wave amplitudes compared to dim light exposure, but that this effect was diminished by TUDCA treatment. Similar effects were seen at all three times post–exposure.
Conclusions: :
These data indicate that TUDCA treatment prevents photoreceptor cell apoptosis, ONL thinning, and retinal function deficits induced by bright light exposure.
Keywords: apoptosis/cell death • pharmacology • degenerations/dystrophies