Autoantibody Profile against Retinal Proteins in Patients with Age-related Macular Degeneration and Antienzymatic Activities

Abstract

Purpose: : To reveal an anti-retinal antibody profile in sera from patients with age-related macular degeneration (AMD) and investigate the pathogenic role of IgGs purified from AMD patients.

Methods: : Serum samples from patients with AMD and normal controls were tested in mass spectrometry analysis following immunoblots against mouse retinal tissue lysates and incubated with an antigen microarray printed with representative retinal proteins to quantify reactivities. Cut-off values for each antibody reactivity were determined by receiver operating characteristic (ROC) analysis. Expression of autoantigens in mouse retina was investigated using Real-time PCR and immunohistochemistry. IgG fractions purified from AMD patients were also tested by enzyme inhibition assay.

Results: : Sera from the AMD group contained high levels of IgG autoantibodies against numerous retinal proteins including lipoproteins, collagens and metabolic enzymes, when compared to the normal control group. Differences in autoantibody profiles were also observed between different stages of the disease, i.e. between dry and wet AMD. Moreover, IgG fractions purified from sera of AMD patients inhibited activities of several enzymes.

Conclusions: : Sera from patients with AMD contain specific autoantibodies which may be used as biomarkers for AMD, and the IgGs purified from AMD patients might be involved in pathogenesis of AMD and retinal aging through inhibition of retinal enzymes.

Keywords: age-related macular degeneration • proteomics • autoimmune disease