Apolipoprotein B in Cholesterol-Containing Drusen and Basal Deposits of Human Eyes with Age-Related Maculopathy
Open accessAbstract
Lipids accumulate in Bruch's membrane (BrM), a specialized vascular intima of the eye, and in extracellular lesions associated with aging and age-related maculopathy (ARM). We tested the hypothesis that ARM and atherosclerotic cardiovascular disease share molecules and mechanisms pertaining to extracellular lipid accumulation by localizing cholesterol and apolipoprotein B (apo B) in BrM, basal deposits, and drusen. Human donor eyes were preserved <4 hours postmortem and cryosectioned. Sections were stained with traditional lipid stains and filipin for esterified and unesterified cholesterol or probed with antibodies to apo B, apo E, and apo C-III. Normal adult retinal pigment epithelium (RPE) was subjected to RT-PCR and Western blot analysis for apolipoprotein mRNA and protein. Esterified and unesterified cholesterol was present in all drusen and basal deposits of ARM and normal eyes. Both apo B and apo E but not apo C-III were found in BrM, drusen, and basal deposits. Fewer macular drusen were stained by traditional lipid stains and apolipoprotein antibodies than peripheral drusen. RPE contained apo B and apo E mRNA and protein. Finding cholesterol and apo B in sub-RPE deposits links ARM with important molecules and mechanisms in atherosclerosis initiation and progression. The combination of apo B mRNA and protein in RPE raises the possibility that intraocular assembly of apo B-containing lipoproteins is a pathway involved in forming cholesterol-enriched lesions in ARM.
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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 [106]
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Bruch’s Membrane and the Choroid in Age-Related Macular Degeneration
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Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium
FROST, L. S., LOPES, V. S., STEFANO, F. P., BRAGIN, A., WILLIAMS, D. S., MITCHELL, C. H., & BOESZE-BATTAGLIA, K. (2013) · Visual Neuroscience · doi:10.1017/s0952523813000096 · Cited by 9 · see citing works
- Authors
- Malek, G., Li, C.-M., Guidry, C., Medeiros, N. E., & Curcio, C. A.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Curcio, Christine A.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 162
- Issue
- 2
- Pages
- 413-425
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1851166
- OpenAlex
- W1999383714
- Cited by
- 270
- References
- 81
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 19 · 2023: 6 · 2022: 8 · 2021: 11 · 2020: 7 · 2019: 10 · 2018: 12 · 2017: 11 · 2016: 5 · 2015: 9 · 2014: 14 · 2013: 11 · 2012: 10
- FWCI
- 17.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (EY06109, T32-EY07033, EY13258)
- International Retinal Research Foundation
- Research to Prevent Blindness
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein B, age-related maculopathy, drusen, Bruch's membrane, cholesterol accumulation, apolipoprotein E, apolipoprotein C-III, retinal pigment epithelium, atherosclerosis, lipoprotein assembly, macular lesions
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Amino Acid Sequence, Apolipoproteins B, Apolipoproteins C, Apolipoproteins E, Cholesterol, Female, Humans, Macular Degeneration, Male, Pigment Epithelium of Eye, Reference Values, RNA, Messenger, Retinal Drusen, Fluorescent Antibody Technique, Indirect, Reverse Transcriptase Polymerase Chain Reaction, Apolipoprotein C-II
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