Human Ocular Drusen Possess Novel Core Domains with a Distinct Carbohydrate Composition

Abstract

SUMMARY Ocular drusen are extracellular deposits that form between the retinal pigmented epithelium (RPE) and Bruch's membrane. Although the presence of large and/or numerous drusen in the macula is a significant risk factor for development of age-related macular degeneration (AMD), a major cause of irreversible blindness, little is known about their origin or composition. We have expanded on our previous investigations related to drusen-associated glycoconjugates by examining lectin binding patterns after removal of terminal sialic acid residues. Strikingly, intense and distinct labeling of drusen subdomains is revealed by Arachea hypogea agglutinin (PNA) after neuraminidase treatment. PNA binding is confined to discrete domains within both hard and soft drusen. These "cores" are positioned centrally within drusen and are typically juxtaposed to Bruch's membrane. Only one core per druse is observed. PNA labeling of drusen cores does not co-localize with associated lipids and is abrogated by digestion with O-glycosidase but not N-glycosidase. The association of cores with small drusen suggests that they may participate in drusen biogenesis. (J Histochem Cytochem 47:1533-1539, 1999)

Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits

“…This evidence and the results of our study suggest that overloading of lipofuscin, the stagnation of subsequently deposited lipofuscin, or both, and insufficiently digested macromolecules on Bruch's membrane without passive diffusion, may trigger a local inflammatory reaction associated with drusen biogenesis. It has been reported that drusen sometimes possesses the core domain composed of carbohydrate at the side of Bruch's membrane [71]. In our model, glycox-MS surrounded or was beneath drusen-like deposits.…”

Angiography features of early onset drusen

“…The difference in lipid composition between the core and the edge of the drusen could be responsible for these patterns of staining. Several studies have shown that AMD drusen possess a central distinct structural core domain, surrounded by a cholesteryl ester shell 13 14. A core-like structure was also described for BLD 15 16.…”

Association between dietary glycemic index and age-related macular degeneration in nondiabetic participants in the Age-Related Eye Disease Study

“…Second, all forms of drusen appear to have similar carbohydrate components and AGE accumulate in drusen with age and occur at a higher level in patients with advanced AMD (41). Third, a high-GI diet has been proposed to play a role in producing oxidative stress and exacerbating proinflammatory processes (19,23,42,43).…”