Age-related macular degeneration (AMD) is the most common cause of vision loss in the elderly population in developed countries. Over a third of those over 75 years currently have some form of this disease. AMD is a progressive, multifactorial, polygenic disease with poorly understood etiology. Genetic evidence now supports an association between AMD susceptibility and variants in genes encoding several complement components and a heat shock serine protease. These associations implicate inflammatory processes in the pathophysiology and we hypothesize that oxidative protein modifications may be initiators of such processes. We have found higher levels of carboxyethylpyrrole (CEP) protein modifications in ocular tissues from AMD than from age-matched normal human donors (1) and elevated CEP adducts and CEP autoantibodies in the plasma of AMD donors (2). CEP adducts are uniquely derived from oxidation of docosahexaenoate (DHA)-containing lipids which are abundant in the retina. CEP adducts can also induce new blood vessel growth in vivo, suggesting oxidative protein modifications may contribute to choroidal neovascularization which accounts for >80percent of vision loss in AMD (3). Here we present progress in our ongoing efforts to identify biomarkers in the blood of individuals susceptible to developing AMD that will allow the identification of those at risk prior to clinical evidence of the disease.
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