Abstract
Purpose: :
Zinc oxide (ZnO), present in the AREDS formulation, may contribute to the long term survival of retinal photoreceptors. In this study we tested ZnO for efficacy in preventing visual cell loss in an acute retinal light damage animal model.
Methods: :
Male Sprague-Dawley rats (P60) were treated with various concentrations of ZnO and then exposed to intense visible light (1200 lux; 490-580 nm) for as long as 8 hours. Typically, light exposure started at 9 am with a ZnO (1xIP) and vehicle (water, pH 3) treated rat in each of 4 green Plexiglas chambers. Following a 14 day dark recovery period, the extent of photoreceptor cell survival was determined by measuring rhodopsin and retinal DNA. Drug efficacy was calculated from the relative levels of visual cell survival in light exposed rats versus dark maintained control animals. Western analysis and histology were used to assess the extent of oxidative stress in the retina and to confirm visual cell survival. Zinc levels were measured in serum and, following animal perfusion with saline, in retinas at various times after injection.
Results: :
In dark reared rats exposed to intense light for 4 hours ZnO was effective at doses greater than 2.6 mg/kg, twice the normal daily AREDS dose. The efficacy of ZnO treatment was about 50% at the dose of 2.6 mg and over 80% for a dose of 7 mg/kg. ZnO was effective for as long as 8 hours when given 1 hour before light exposure, but much less effective 1 hour after the onset of light. Serum levels of Zn increased over 3 fold, reaching 7.6 µg/ml 1 hour after injection, and remained elevated 4 hours thereafter. Zinc levels were about 0.12 µg/retina in both treated and untreated animals. Retinal histology confirmed that rod photoreceptors were preserved by ZnO treatment.
Conclusions: :
Zinc is a component in the AREDS formulation that provides protection against acute light induced retinal degeneration. ZnO treatment was effective for at least 8 hours of light exposure. Zinc’s protective efficacy might arise from induction of antioxidative enzymes or from ionic effects in retinal tissues.
Keywords: oxidation/oxidative or free radical damage • radiation damage: light/UV • photoreceptors