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(The FASEB Journal. 2000;14:835-846.)
© 2000 FASEB

Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease

ROBERT F. MULLINS, STEPHEN R. RUSSELL, DON H. ANDERSON* and GREGORY S. HAGEMAN1

The University of Iowa Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa 52242, USA; and
* Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA

1Correspondence: Department of Ophthalmology and Visual Sciences, The University of Iowa, 11190E PFP, 200 Hawkins Dr., Iowa City, Iowa 52240, USA. E-mail address: gregory-hageman{at}uiowa.edu

Age-related macular degeneration (AMD), a blinding disorder that compromises central vision, is characterized by the accumulation of extracellular deposits, termed drusen, between the retinal pigmented epithelium and the choroid. Recent studies in this laboratory revealed that vitronectin is a major component of drusen. Because vitronectin is also a constituent of abnormal deposits associated with a variety of diseases, drusen from human donor eyes were examined for compositional similarities with other extracellular disease deposits. Thirty-four antibodies to 29 different proteins or protein complexes were tested for immunoreactivity with hard and soft drusen phenotypes. These analyses provide a partial profile of the molecular composition of drusen. Serum amyloid P component, apolipoprotein E, immunoglobulin light chains, Factor X, and complement proteins (C5 and C5b-9 complex) were identified in all drusen phenotypes. Transcripts encoding some of these molecules were also found to be synthesized by the retina, retinal pigmented epithelium, and/or choroid. The compositional similarity between drusen and other disease deposits may be significant in view of the recently established correlation between AMD and atherosclerosis. This study suggests that similar pathways may be involved in the etiologies of AMD and other age-related diseases.—Mullins, R. F., Russell, S. R., Anderson, D. H., Hageman, G. S. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease.


Key Words: retina • retinal pigmented epithelium • amyloid • vitronectin • soft drusen




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