Similarities in Plasma Oxidative Modifications From Retinal Light Damage and AMD

Abstract

Abstract: : Purpose:To identify similarities in pathogenesis between age–related macular degeneration (AMD) and retinal light damage and to identify biomarkers for AMD, we measured plasma carboxyethylpyrrole (CEP) and ethylpyrrole (EP) adducts and autoantibodies. CEP and EP adducts are generated from the oxidation of docosahexaenoate (DHA)–containing lipids. Methods:Blood was collected from clinically documented AMD and normal, healthy donors at the Cleveland Clinic Foundation and Louis Stokes VA Medical Center. Dark adapted albino rats with or without pretreatment with dimethyl thiourea (DMTU) were exposed to intense green light (1500 lux) for 0, 2, 4, or 8h then sacrificed. Blood was drawn immediately, antioxidants added and plasma prepared. Plasma CEP and EP immunoreactivities and autoantibody titers were measured by ELISA. Results:Rat plasma CEP immunoreactivity and autoantibody titer increased with light exposure and after 8h were ∼1.6x and ∼2.8x higher, respectively, without DMTU (n = 6 per time point). With DMTU, CEP values were lower. Rat plasma EP values did not change significantly with light exposure. However, human EP immunoreactivity was ∼1.4x greater in AMD plasma (n = 51) relative to normal donors (n = 22). Statistically significant elevation of EP immunoreactivity was observed in human plasma from AREDS AMD category 2 (n = 20), but not in AMD category 3 (n = 17) or AMD category 4 (n = 14). Conclusions: Elevated CEP immunoreactivity and autoantibody titer in plasma from both light damaged rats and AMD donors support DHA oxidation as a common mechanism of pathogenesis. The lack of elevated EP in light damaged rat plasma and late stage AMD may reflect further modification of EP due to more acute damage. Nevertheless, plasma EP may have utility as an AMD biomarker.

Keywords: age-related macular degeneration • oxidation/oxidative or free radical damage • protein modifications-post translational