Biomarkers for Age–Related Macular Degeneration

Abstract

Abstract: : Purpose: To develop a blood test for biomarkers of AMD susceptibility that will allow identification of individuals at risk for age–related macular degeneration (AMD) prior to macular degeneration and vision loss. Validation studies are in progress testing carboxyethylpyrrole (CEP) immunoreactivity and autoantibodies as possible predictors of AMD susceptibility. CEP protein adducts are generated from oxidative fragmentation of docosahexaenoate–containing lipids and are elevated in AMD ocular tissues (2002 Proc Natl Acad Sci USA 99, 14282) Methods: Blood was collected from patients with geographic atrophy or choroidal neovascularization secondary to age–related macular degeneration and from normal, healthy donors at the Cole Eye Institute, Cleveland Clinic Foundation. Plasma CEP immunoreactivity and CEP autoantibody titer were determined by ELISA using rabbit polyclonal anti–CEP antibody and CEP modified albumin as a reference standard. Results:Consistent with preliminary results (2003 J Biol Chem 278, 42027), plasma from additional AMD patients (n = 12 donors) exhibited higher mean levels of anti–CEP autoantibody and anti–CEP immunoreactivity relative to additional normal controls (n = 12 donors). Of individuals exhibiting both antigen and autoantibody levels above the mean for non–AMD controls (n =10), 80% had AMD. The data further support a higher probability of correctly predicting AMD using both CEP immunoreactivity and CEP autoantibody titer than using either variable alone. Conclusions: Preventing age–related macular degeneration is an important public health goal. Identifying patients at risk for developing this disease is an important first step. A combination of plasma CEP immunoreactivity and autoantibody titer may have prognostic utility in identifying those most susceptible to developing AMD. Progress in this on going validation study will be presented..

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