Orally Active Multi-functional Antioxidants Reduce Light-induced Retinal Damage In Rats

Abstract

Purpose: : Light-induced retinal damage, which is associated with oxidative stress and iron release, is an animal model for the dry form of AMD. Here, we determined whether orally active multi-functional antioxidants that can independently scavenge free radicals and chelate unbound redox-active metals can ameliorate light-induced retinal degeneration in rats.

Methods: : Three groups of young Wistar rats were housed in dim light (5 lx). One group served as control while the other two groups were fed rodent chow supplemented with 0.05% of either multi-functional compound JHX-4 or JHX-8. After two weeks, 12 rats from each group were exposed to 1000 lx light for 3 h. After exposure, eyes from 8 light exposed and 8 non-exposed rats from each group were immediately evaluated for retinal oxidative stress markers measured by ELISA and western blot. The remaining light exposed rats from each group were returned to the dim light environment. After an additional 5-7 days of dark adaptation, the retinal functions in all remaining rats from each group were assessed by ERG followed by histological evaluation of the thickness of the outer nuclear layer (photoreceptor layer).

Results: : Assessment of the oxidative stress markers 4-hydroxynonenal modified proteins and thioredoxin indicated that these multi-functional compounds reduced/normalized the oxidative insult caused by light exposure. In the ERG analyses, light exposure to the untreated rats resulted in a significant reduction in ERG scotopic a- and b-wave amplitudes (30 and 25%, respectively) and a 22% reduction in photopic b-wave amplitude compared to untreated, dark-adapted rats. No reduction in maximum ERG amplitude was observed in similar rats treated with either JHX-4 or JHX-8. This protection of the rods and cones was confirmed by histological evaluation of H & E stained paraffin sections of the retina through the optic disk.

Conclusions: : Retinal neuroprotection by the multi-functional antioxidants JHX-4 or JHX-8 was observed by biochemical analysis, ERG waveform measurements, and histology. While this study suggests that the multi-functional antioxidants may be beneficial for treating AMD, further investigations with other animal models of AMD are required.

Keywords: age-related macular degeneration • retina: distal (photoreceptors, horizontal cells, bipolar cells) • oxidation/oxidative or free radical damage