Soluble and Mature Amyloid Fibrils in Drusen Deposits

PURPOSE. Drusen are a hallmark of eyes affected by age-related macular degeneration. In previous study, a conformational-specific antibody showed drusen to contain nonfibrillar amyloid structures. The current study was undertaken to assess the presence of additional amyloid structures in drusen. METHODS. Sections from human donor eyes were reacted with M204, a monoclonal antibody that recognizes nonfibrillar oligomers; OC, a polyclonal antibody that recognizes amyloid fibrils of various molecular weights; and WO1 and WO2, monoclonal antibodies that are specifically reactive to mature amyloid fibrils. Electron microscopy was used as an independent means of investigating the presence of amyloid fibrils in drusen. RESULTS. The presence of nonfibrillar oligomers was verified using the M204 antibody. OC and WO antibodies stained a wide spectrum of vesicular structures. OC reactivity showed extensive overlap with A beta immunoreactivity, whereas a partial overlap was seen between A beta reactivity and that of the WO antibodies. The presence of amyloid fibrils was also visualized by electron microscopy. CONCLUSIONS. These data reveal the presence of a wide spectrum of amyloid structures in drusen. The results are significant, given that specific conformational forms of amyloid are known to be pathogenic in a variety of neurodegenerative diseases. Deposition of these structures may lead to local toxicity of the retinal pigmented epithelium or induction of local inflammatory events that contribute to drusen biogenesis and the pathogenesis of AMD. (Invest Ophthalmol Vis Sci. 2010;51:1304-1310) DOI:10.1167/iovs.09-4207