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Cited by 1,087Retinal Diseases and TreatmentsOcular Diseases and Behçet’s SyndromeRetinal Imaging and Analysis

A role for local inflammation in the formation of drusen in the aging eye

Anderson, Don H, Mullins, Robert F, Hageman, Gregory S, Johnson, Lincoln V·2002·American Journal of Ophthalmology
DOI 10.1016/s0002-9394(02)01624-0
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Abstract

Purpose The accumulation of numerous or confluent drusen, especially in the macula, is a significant risk factor for the development of age-related macular degeneration (AMD). Identifying the origin and molecular composition of these deposits, therefore, has been an important, yet elusive, objective for many decades. Recently, a more complete profile of the molecular composition of drusen has emerged.Design In this focused review, we discuss these new findings and their implications for the pathogenic events that give rise to drusen and AMD.Methods Tissue specimens from one or both eyes of more than 400 human donors were examined by light, confocal or electron microscopy, in conjunction with antibodies to specific drusen-associated proteins, to help characterize the transitional events in drusen biogenesis. Quantification of messenger RNA from the retinal pigment epithelium (RPE)/choroid of donor eyes was used to determine if local ocular sources for drusen-associated molecules exist.Results The results indicate that cellular remnants and debris derived from degenerate RPE cells become sequestered between the RPE basal lamina and Bruch's membrane. We propose that this cellular debris constitutes a chronic inflammatory stimulus, and a potential "nucleation" site for drusen formation. The entrapped cellular debris then becomes the target of encapsulation by a variety of inflammatory mediators, some of which are contributed by the RPE and, perhaps, other local cell types; and some of which are extravasated from the choroidal circulation.Conclusions The results support a role for local inflammation in drusen biogenesis, and suggest that it is analogous to the process that occurs in other age-related diseases, such as Alzheimer's disease and atherosclerosis, where accumulation of extracellular plaques and deposits elicits a local chronic inflammatory response that exacerbates the effects of primary pathogenic stimuli.

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Crossref · 10.1016/s0002-9394(02)01624-0

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106 of 106 references verified0 citation errors · 0 not checkable

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  • The presence of an inflammatory cell component at the site of breaks in Bruch's membrane strongly suggests that the immune system is intricately involved in disease progression.

    “The presence of an inflammatory cell component at the site of breaks in Bruch’s membrane strongly suggests that the immune system is intricately involved in disease progression (van der Schaft et al., 1992; Spraul and Grossniklaus, 1997; Anderson et al., 2002; Chan et al., 2008; Patel and Chan, 2008).”

    From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Anderson et al., 2002

  • Macrophages have been documented both morphologically and functionally in neovascular age-related macular degeneration.

    “Macrophages have been documented both morphologically and functionally in neovascular age-related macular degeneration.137–142”

    From Age-related macular degeneration (2008) · cites this paper as [142]

  • 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 [6]

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Authors
Anderson, D. H., Mullins, R. F., Hageman, G. S., & Johnson, L. V.
Affiliations
  • University of California, Santa Barbara (US)
  • University of Iowa (US)
Corresponding author
Anderson, Don H
ORCID
Venue
American Journal of Ophthalmology
Publisher
Elsevier BV
Published
2002-09
Volume
134
Issue
3
Pages
411-431
ISSN
0002-9394 (ISSN-L)
DOI
10.1016/s0002-9394(02)01624-0
OpenAlex
W2088551743
Cited by
1,087
References
106
Citations by year
2026: 14 · 2025: 32 · 2024: 45 · 2023: 24 · 2022: 37 · 2021: 56 · 2020: 48 · 2019: 36 · 2018: 38 · 2017: 60 · 2016: 47 · 2015: 64 · 2014: 56 · 2013: 63 · 2012: 71
FWCI
6.16
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • American Journal of Ophthalmology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Eye Institute (EY11515, R01EY011521, EY 11-521, R01EY011527, R01EY011515, EY11527)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords
drusen, age-related macular degeneration, local inflammation, retinal pigment epithelium, Bruch's membrane, choroid, chronic inflammation, ocular aging
MeSH terms
Aging, Eye Proteins, Humans, Macular Degeneration, Pigment Epithelium of Eye, Retinitis, RNA, Messenger, Retinal Drusen, Microscopy, Confocal

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