Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease
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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. FASEB J. 14, 835–846 (2000)
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Apolipoproteins B and E, immunoglobulins, factor X, amyloid P component, amyloid β, complement C5 and C5b-9 terminal complexes, fibrinogen, and vitronectin are present in all phenotypes of hard and soft drusen.
“Immunohistochemical analyses have shown various molecular constituents, such as apolipoproteins B and E, different immunoglobulins, factor X, amyloid P component, amyloid β, complement C5 and C5b-9 terminal complexes, fibrinogen, vitronectin, and others, to be present in all phenotypes of hard and soft drusen”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Mullins et al., 2000
Carboxyethyl pyrrole immunoreactive proteins in AMD Bruch's membrane include albumin and alpha-1-antitrypsin.
“Among the nine identified immunopositive proteins were albumin and 𝛂 1-antitrypsin, both of which were detected in drusen by LC MS ∕ MS (Table 3) and immunocytochemistry (14).”
From Drusen proteome analysis: an approach to the etiology of age-related macular degeneration (2002) · cites this paper as [14]
Biochemical analysis of drusen has identified glycoconjugates and components found in atherosclerotic plaques, including vitronectin, apolipoprotein B and E, alpha-crystallin, complement proteins, and lipids.
“Biochemical analysis of drusen has identified glycoconjugates and components found in atherosclerotic plaques including vitronectin, apolipoprotein B and E, alpha-crystallin, complement proteins, and lipids (32, 106, 115).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [115]
Drusen contain acute phase proteins, complement pathway components and inhibitors, apolipoproteins B and E, mucopolysaccarides, lipids, mannose, and sialic acid.
“Studies analyzing the composition of drusen have shown that drusen contain acute phase proteins (C-reactive protein, vitronectin, α-antichymotrypsin, amyloid P component, and fibrinogen), complement pathway components (C3, C5 and C5b-9 complex) and inhibitors (clusterin), apolipoproteins B and E, mucopolysaccarides, lipids, mannose, and sialic acid (Farkas et al., 1971; Mullins et al., 2000).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Mullins et al., 2000
cfh−/− mice have C3 accumulation in the retina, secondary C3 deficiency, and uncontrolled C3 activation.
“The cfh−/− mice had C3 accumulation in the retina, secondary C3 deficiency, and uncontrolled C3 activation, which may increase phagocytic uptake and cause neural damage to the retina (Mullins et al., 2000; Coffey et al., 2007).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Mullins et al., 2000
In Ccl2−/− mice, deposition of IgG, C5, vitronectin, CD46, serum amyloid P, and advanced glycosylation endproducts was present in a distribution similar to human AMD eyes.
“In this model, deposition of IgG, C5, vitronectin, CD46, serum amyloid P, and advanced glycosylation endproducts were present in Ccl2−/− mice in a distribution similar to what has been previously reported in humans AMD eyes (Ambati et al., 2003; Mullins et al., 2000).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Mullins et al., 2000
Biochemical analysis of drusen has identified complement components and inflammatory modulators.
“Biochemical analysis of drusen have indeed resulted in identification of complement components and inflammatory modulators [2–8].”
From CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD (2005) · cites this paper as [4]
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- Authors
- Mullins, R. F., Russell, S. R., Anderson, D. H., & Hageman, G. S.
- Affiliations
- University of Iowa (US)
- University of California, Santa Barbara (US)
- Corresponding author
- Hageman, Gregory S.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2000-05
- Volume
- 14
- Issue
- 7
- Pages
- 835-846
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1883306593
- Cited by
- 937
- References
- 110
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 29 · 2023: 28 · 2022: 36 · 2021: 40 · 2020: 41 · 2019: 23 · 2018: 33 · 2017: 44 · 2016: 35 · 2015: 44 · 2014: 48 · 2013: 59 · 2012: 42
- FWCI
- 25.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH Office of the Director (EY06463, EY11515, EY11521, AG00214)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- drusen, age-related macular degeneration, vitronectin, atherosclerosis, elastosis, amyloidosis, dense deposit disease, serum amyloid P component, apolipoprotein E, immunoglobulin light chains, factor X, complement C5, complement C5b-9, retinal pigment epithelium, choroid, aging, protein composition
- MeSH terms
- Aging, Amyloidosis, Arteriosclerosis, Base Sequence, Humans, Immunohistochemistry, Macular Degeneration, Proteins, RNA, Messenger, Skin Diseases, Glomerulonephritis, Membranoproliferative, Retinal Drusen, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction
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