Abstract
Purpose:
While hops is commonly recognized as an ingredient of beer, one of its lesser-known constituents, the flavonoid derivative xanthohumol (Xn), has been shown to scavenge reactive oxygen species. If xanthohumol can mitigate oxidative damage in the eye, it may be a valuable treatment for retinal degenerations. In this experiment, we sought to test the ability of xanthohumol to preserve vision in the light-induced retinal degeneration (LIRD) mouse, an environmental model of blindness.
Methods:
Twelve male 129SV mice (Charles River Laboratory) were given two intraperitoneal injections of Xn (0.8 mg/kg) or vehicle (4 PBS: 1 ethanol: 1 cremophor) prior to light damage. Atropine eye drops (1%) were administered twice before light damage to dilate pupils. Bright Xn and bright vehicle treatment groups were exposed to 50,000 lux of white LED light for 6 hours, while dim Xn and dim vehicle groups received 50 lux of normal light. After light damage, injections were administered five times per week to maintain systemic drug levels. To assess visual function and acuity, optokinetic tracking (OKT) and electroretinograms (ERGs) were performed once weekly after light damage.
Results:
Mean ERG b-wave amplitudes were significantly higher for bright Xn mice as compared to bright vehicle, with representative amplitudes (in microvolts ± SEM) of 445±62 and 263±29, respectively, at a flash intensity of 24.9 cd s/m2 (P<0.05). Mean b-wave amplitudes for dim Xn and dim vehicle were 491±37 and 539±62. Visual acuity as measured by OKT was significantly higher in bright Xn mice as compared to bright vehicle at two weeks post-LIRD. Acuity measurements two weeks after light damage for bright Xn and bright vehicle mice were 0.493±0.032 and 0.373±0.016 (P<0.05). Statistical analysis was performed by one-way ANOVA-SNK for ERG and OKT values. The same treatment effect was observed in a replicate experiment (n=3 per group for each of the experiments).
Conclusions:
Systemic injection of Xn resulted in significant preservation of visual function and acuity in the LIRD mouse. This is the first report of xanthohumol being used as a neuroprotectant for retinal degenerations. Future work will investigate the mechanistic actions of xanthohumol to determine its method of protection.
Keywords: 695 retinal degenerations: cell biology •
615 neuroprotection •
426 apoptosis/cell death