Morphometric Analysis of Lipoprotein-like Particle Accumulation in Aging Human Macular Bruch’s Membrane
Open accessAbstract
PURPOSE: To determine the size and regional distribution of lipoprotein-like particles (LLPs) that accumulate with age in Bruch's membrane (BrM). METHODS: The quick-freeze/deep-etch method was used to prepare specimens of human BrM (age range, 27-78) for electron microscopic examination. Stereologic methods were used to analyze the resultant micrographs and determine the age-related changes of the LLP volume fraction and diameter distribution in various locations in BrM. RESULTS: The volume fraction occupied by LLPs was found to increase monotonically with age in both the inner collagenous layer (ICL) and elastic layer (EL), but not in the outer collagenous layer (OCL). The mass of total LLP-associated lipids in BrM also increased with age. There was no significant increase in LLP size with age, but there was a modest increase in size with increased volume fraction of LLPs in BrM. CONCLUSIONS: The pattern of accumulation of particles was consistent with a retinal pigment epithelium (RPE) source for the LLPs, which explains why once the EL and ICL were filled with particles, LLPs continued to accumulate near the RPE, but no further accumulation was found in the OCL. The quantity of LLP-associated lipids found in BrM accounts for a large portion of the accumulated lipids measured in this tissue.
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Older individuals commonly have small drusen beneath the retina and cholesterol accumulation in Bruch's membrane.
“Older individuals commonly have small drusen beneath the retina and cholesterol accumulation in Bruch’s membrane (64, 74).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [74]
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Cites
Tietz Textbook of Clinical Chemistry
(1999) · Archives of Pathology & Laboratory Medicine · doi:10.5858/123.7.646b · Cited by 2,518 · see citing works
Ageing and degeneration in the macular region: A clinico-pathological study
Sarks, S. H. (1976) · British Journal of Ophthalmology · doi:10.1136/bjo.60.5.324 · Cited by 891 · see citing works
Accumulation of cholesterol with age in human Bruch's membrane.
Curcio, C. A., Millican, C. L., Bailey, T. A., & Kruth, H. S. (2001) · PubMed · Cited by 442 · see citing works
Self-citationAging changes in Bruch's membrane. A histochemical and morphologic study.
Pauleikhoff, D., Harper, C. A., Marshall, J., & Bird, A. C. (1990) · PubMed · Cited by 401 · see citing works
Ocular Biomechanics and Biotransport
Ethier, C. R., Johnson, M. F., & Ruberti, J. (2004) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.6.040803.140055 · Cited by 290 · see citing works
Self-citationAnalysis of Lipid Deposits Extracted From Human Macular and Peripheral Bruch's Membrane
Holz, F. G. (1994) · Archives of Ophthalmology · doi:10.1001/archopht.1994.01090150132035 · Cited by 260 · see citing works
Chapman, M. J., Laplaud, P. M., Luc, G., Forgez, P., Bruckert, E., Goulinet, S., & Lagrange, D. (1988) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38518-7 · Cited by 216 · see citing works
Retinal pigment epithelial detachments in the elderly.
Bird, A. C., & Marshall, J. (1986) · PubMed · Cited by 191 · see citing works
The retinal pigment epithelium : function and disease
Marmor, M. F., & Wolfensberger, T. J. (1998) · Cited by 185 · see citing works
Basal deposits and drusen in eyes with age-related maculopathy: Evidence for solid lipid particles
Curcio, C. A., Presley, J. B., Millican, C. L., & Medeiros, N. E. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2004.09.017 · Cited by 171 · see citing works
Self-citationHydrodynamics of ageing Bruch’s membrane: Implications for macular disease
STARITA, C., HUSSAIN, A. A., PAGLIARINI, S., & MARSHALL, J. (1996) · Experimental Eye Research · doi:10.1006/exer.1996.0066 · Cited by 170 · see citing works
Functional loss in age-related Bruch's membrane change with choroidal perfusion defect.
Chen, J. C., Fitzke, F. W., Pauleikhoff, D., & Bird, A. C. (1992) · PubMed · Cited by 165 · see citing works
Li, C., Chung, B. H., Presley, J. B., Malek, G., Zhang, X., Dashti, N., Li, L., Chen, J., Bradley, K. M., Kruth, H. S., et al. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-0034 · Cited by 151 · see citing works
Self-citationQuick-Freeze/Deep-Etch Visualization of Age-Related Lipid Accumulation in Bruch’s Membrane
Ruberti, J. W., Curcio, C. A., Millican, C. L., Menco, B. P. M., Huang, J.-D., & Johnson, M. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-0496 · Cited by 139 · see citing works
Self-citationHaimovici, R., Gantz, D., Rumelt, S., Freddo, T. F., & SMALL, D. M. (2001) · PubMed · Cited by 129 · see citing works
Ageing changes in Bruch's membrane and their functional implications.
Cf, G., & Marshall, J.-C. (1978) · PubMed · Cited by 111 · see citing works
Age-related changes in human macular Bruch's membrane as seen by quick-freeze/deep-etch
Huang, J.-D., Presley, J. B., Chimento, M. F., Curcio, C. A., & Johnson, M. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2007.03.011 · Cited by 102 · see citing works
Self-citationComparison of Morphology of Human Macular and Peripheral Bruch's Membrane in Older Eyes
Johnson, M., Dabholkar, A. S., Huang, J.-D., Presley, J. B., Chimento, M. F., & Curcio, C. A. (2007) · Current Eye Research · doi:10.1080/02713680701550660 · Cited by 41 · see citing works
Self-citationSpecific Hydraulic Conductivity of Corneal Stroma as Seen by Quick-Freeze/Deep-Etch
Overby, D. R., Ruberti, J. W., Gong, H., et al. (2000) · Journal of Biomechanical Engineering · doi:10.1115/1.1351888 · Cited by 36 · see citing works
Relationship between Plasma Lipids and Arterial Tissue Lipids
Smith, E. B., & Slater, R. S. (1973) · Annals of Nutrition and Metabolism · doi:10.1159/000175418 · Cited by 30 · see citing works
Studies on depth‐of‐field effects in microscopy supported by numerical simulations
Overby, D. R., & Johnson, M. F. (2005) · Journal of Microscopy · doi:10.1111/j.1365-2818.2005.01520.x · Cited by 22 · see citing works
Self-citationSchmitz, G., Assmann, G., Augustin, J., Dirkes-Kersting, A., Brennhausen, B., & Karoff, C. (1985) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)34374-1 · Cited by 22 · see citing works
Tso, P., Ragland, J. B., & Sabesin, S. M. (1983) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37926-8 · Cited by 20 · see citing works
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Booij, J. C., Baas, D. C., Beisekeeva, J., Gorgels, T. G. M. F., & Bergen, A. A. B. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.08.003 · Cited by 581 · see citing works
Swaroop, A., Chew, E. Y., Bowes Rickman, C., & Abecasis, G. R. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164350 · Cited by 270 · see citing works
A new perspective on lipid research in age-related macular degeneration
van Leeuwen, E. M., Emri, E., Merle, B. M. J., Colijn, J. M., Kersten, E., Cougnard-Gregoire, A., Dammeier, S., Meester-Smoor, M., Pool, F. M., de Jong, E. K., et al. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.04.006 · Cited by 247 · see citing works
Lee, Y., Hussain, A. A., Seok, J.-H., Kim, S.-H., & Marshall, J. (2015) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.15-16936 · Cited by 26 · see citing works
- Authors
- Huang, J.-D., Curcio, C. A., & Johnson, M.
- Affiliations
- Northwestern University (US)
- University of Alabama (US)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2008-06-01
- Volume
- 49
- Issue
- 6
- Pages
- 2721
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC2504737
- OpenAlex
- W1984366160
- Cited by
- 47
- References
- 23
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY-014662, R01EY006109, R01EY014662, EY06109)
- National Center for Research Resources (S10RR016701)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
- Keywords
- Bruch's membrane, aging, macula, retinal pigment epithelium, lipoprotein accumulation, lipid accumulation, elastic layer, particle size distribution, volume fraction, stereology
- MeSH terms
- Adult, Aged, Aging, Cytoplasmic Granules, Eye Proteins, Female, Freeze Etching, Humans, Image Processing, Computer-Assisted, Lipoproteins, Macula Lutea, Macular Degeneration, Male, Middle Aged, Bruch Membrane, Lipid Metabolism
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