Abstract
Purpose: :
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly in west countries. Oxygen free radicals have long been suspected as a causative agent, yet its precise cause is still unclear. Lipid peroxidation by reactive oxygen of polyunstaturated fatty acids is believed to play a significant role. Specific compounds however, have not been demonstrated correlated with age of onset, severity or prognosis of AMD. Malondialdehyde (MDA) is a metabolite of lipid peroxidation. The generation of MDA is a reflection of oxidative stress on polyunsaturated fatty acids and is widely accepted as a biomarker for overall lipid peroxidation. The purpose of this study is to link the pathogenesis of AMD to oxidation stress by measuring the levels of MDA in oxidative stressed human retinal pigmented epithelial (RPE) cells. The plasma concentration of MDA has also been determined in human subjects with varying stages of AMD and compared to age, gender-matched normal controls.
Methods: :
Human RPE cells were incubated with different concentrations of the oxidative agent tertiary butyl hydroperoxide (t-BuOOH) in vitro. Following incubation at various time points, the MDA concentration in the culture media were determined by an assay kit supplied by Northwest Life Science Specialties, LLC Kit (Vancouver, Canada). The MDA levels in the plasma of AMD patients and their age and sex-matched healthy controls were also examined by this same assay. Exclusion criteria included diabetic retinopathy and other serious retinal disease. The results were analyzed with Student "t" test.
Results: :
MDA concentration in t-BuOOH treated RPE cells was five times higher (P<0.001) than that of RPE cells without treatment. Such elevation was dose and time-dependent. The plasma levels of MDA in patients suffered with AMD were significantly higher (mean=0.782, n=51) comparing with their age and sex matched controls (mean=0.572, n=37) (P<0.05).
Conclusions: :
These results strongly linked lipid peroxidation of human retina with the pathogenesis of AMD.
Keywords: age-related macular degeneration • oxidation/oxidative or free radical damage • lipids