Abstract
Purpose: :
Photoreceptor degeneration is a major cause of visual loss in various retinal diseases, including retinal detachment (RD) and neovascular AMD, pharmacologic inhibition of photoreceptor cell death may prevent this outcome. This study tests whether systemic administration of Resveratrol can protect photoreceptors from cell death after experimental retinal detachment in rodents.
Methods: :
Retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with vehicle, Resveratrol (20mg/kg) intraperitoneal (IP) injection only or Resveratrol intraperitoneal injection (20mg/kg) with subretinal injection (25 μM). Photoreceptor degeneration was assessed by counting the number of apoptotic cells with TdT-dUTP terminal nick-end labeling (TUNEL) 3 days after RD. Changes in expression of FoxO1A, FoxO3A, and FoxO4 were analyzed by western blot. Caspase 3 and 9 levels were studied as well.
Results: :
Three days after detachment, Resveratrol decreased the number of TUNEL-positive cells in both Resveratrol treatment groups by 71% and 74% compared to vehicle in the IP and IP with subretinal injection, respectively. Retinal detachment increased the expression of FoxO1A, FoxO3A, and FoxO4. Resveratrol treatment significantly increases FoxO4 expression in retinal detachment eyes. The increase in activity of caspase 3 and 9 in retinal detachment was partially inhibited by Resveratrol.
Conclusions: :
Systemic administration of Resveratrol preserved photoreceptors after retinal detachment, and was associated with activation of FoxO family expression and decreased caspase activity. Resveratrol has great potential to be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment.
Keywords: photoreceptors • apoptosis/cell death • retinal detachment