| Age-related macular degeneration, a blinding disorder that affects central vision, is characterized clinically by an accumulation of deposits, termed drusen, between the retinal pigmented epithelium and the choroid. Although drusen are widely regarded as significant risk factors for the development of macular degeneration, little is known about their origin or composition. In an effort develop a greater understanding of the etiology of AMD, we have employed histochemical, immunohistochemical, ultrastructural, and biochemical approaches to characterize drusen. We characterized the carbohydrate profile of hard and soft drusen employing a battery of lectins; drusen possess a distinct array of saccharides which are present in all drusen subclasses. The composition of drusen was further analyzed by screening human donor tissues with antibodies directed against extracellular matrix proteins. Vitronectin was identified as an invariant extracellular matrix component of drusen. This observation led us to examine drusen for the presence of molecular constituents of abnormal deposits associated with other diseases. Amyloid P component, complement complexes, and other disease plaque molecules were identified as major constituents of hard and soft drusen. Collectively, these analyses suggest that the proteinaceous components of hard and soft drusen are similar, and that these clinical categories may not be significant in terms of drusen composition.;Combined histochemical and enzymatic analyses revealed substructural elements, or "cores", within drusen. These cores are present at early stages of drusen formation. Further ultrastructural and immunohistochemical studies of these cores suggest that they are associated with cell processes derived from choroidal cells, and may implicate these cells in drusen formation. We also developed schemes for the enrichment of drusen.;These preparations were utilized in preliminary studies to characterize drusen biochemically. These studies collectively contribute novel information pertaining to drusen origin and composition, and shed new light on the etiology of age-related macular degeneration. |
