Drusen associated with aging and age‐related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease

TLDR

Age‑related macular degeneration is marked by extracellular drusen deposits rich in vitronectin, whose compositional overlap with atherosclerotic and other disease deposits suggests shared pathogenic pathways. The study examined drusen from donor eyes to assess compositional similarities with extracellular deposits from other diseases. Immunostaining with 34 antibodies against 29 proteins was performed on hard and soft drusen to profile their molecular composition. The analysis revealed that all drusen phenotypes contain serum amyloid P, apolipoprotein E, immunoglobulin light chains, Factor X, and complement components C5/C5b‑9, with corresponding transcripts expressed in retinal tissues, indicating shared pathogenic mechanisms with other age‑related diseases.

Abstract

Age-related macular degeneration (AMD), a blinding disorder that compromises central vision, is characterized by the accumulation of extracellular deposits, termed drusen, between the retinal pigmented epithelium and the choroid. Recent studies in this laboratory revealed that vitronectin is a major component of drusen. Because vitronectin is also a constituent of abnormal deposits associated with a variety of diseases, drusen from human donor eyes were examined for compositional similarities with other extracellular disease deposits. Thirty-four antibodies to 29 different proteins or protein complexes were tested for immunoreactivity with hard and soft drusen phenotypes. These analyses provide a partial profile of the molecular composition of drusen. Serum amyloid P component, apolipoprotein E, immunoglobulin light chains, Factor X, and complement proteins (C5 and C5b-9 complex) were identified in all drusen phenotypes. Transcripts encoding some of these molecules were also found to be synthesized by the retina, retinal pigmented epithelium, and/or choroid. The compositional similarity between drusen and other disease deposits may be significant in view of the recently established correlation between AMD and atherosclerosis. This study suggests that similar pathways may be involved in the etiologies of AMD and other age-related diseases.