Robert F. Mullins, Lincoln V. Johnson, Don H. Anderson, Gregory S. Hageman

Drusen are extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium and the elastic lamina of Bruch membrane in aging human eyes. Although specific types of drusen are recognized as significant risk factors for the development of both the atrophic and exudative forms of age-related macular degeneration, few studies have focused on defining their molecular composition. As an initial step toward identifying the molecular composition of drusen, assessing the biochemical relation between hard and soft drusen, and identifying potential target molecules for detecting drusen clinically, the authors have analyzed their carbohydrate composition using lectin histochemistry. Sections of eyes from human donors containing a spectrum of hard and soft drusen were screened with a battery of 22 fluorescein-conjugated lectins. A specific subset of six lectins bind drusen intensely. No significant differences in lectin binding are observed between any subclass of hard and soft drusen. Some drusen exhibit homogeneous, uniform labeling, whereas others show asymmetrical, heterogeneous distribution of glycoconjugates. This study shows that glycoconjugates containing specific carbohydrate residues are present in all classes of hard and soft drusen examined. The observation that hard and soft drusen are bound by the same lectins suggests that they may be related compositionally. Identification of the drusen-associated glycoconjugates shown in this investigation will facilitate studies of drusen genesis and their involvement in the pathogenesis of age-related maculopathy. They may also provide a basis for developing avenues of therapeutic intervention.