CHARACTERIZATION OF DRUSEN-ASSOCIATED GLYCOCONJUGATES

Background: Drusen are extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium and the elastic lam ina 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 degene ration, few studies have focused on defining their molecular compositi on, As an initial step toward identifying the molecular composition of drusen, assessing the biochemical relation between hard and soft drus en, and identifying potential target molecules for detecting drusen cl inically, the authors have analyzed their carbohydrate composition usi ng lectin histochemistry. Methods: Sections of eyes from human donors containing a spectrum of hard and soft drusen were screened with a bat tery of 22 fluorescein-conjugated lectins.Results: A specific subset o f six lectins bind drusen intensely. No significant differences in lec tin binding are observed between any subclass of hard and soft drusen. Some drusen exhibit homogeneous, uniform labeling, whereas others sho w asymmetrical, heterogeneous distribution of glycoconjugates. Conclus ion: This study shows that glycoconjugates containing specific carbohy drate residues are present in all classes of hard and soft drusen exam ined. The observation that hard and soft drusen are bound by the same lectins suggests that they may be related compositionally. Identificat ion of the drusen-associated glycoconjugates shown in this investigati on will facilitate studies of drusen genesis and their involvement in the pathogenesis of age-related maculopathy. They may also provide a b asis for developing avenues of therapeutic intervention.