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Cited by 171Retinal Diseases and TreatmentsRetinal Imaging and AnalysisRetinal Development and Disorders

Basal deposits and drusen in eyes with age-related maculopathy: Evidence for solid lipid particles

Curcio, Christine A., Presley, J. Brett, Millican, C. Leigh, Medeiros, Nancy E.·2005·Experimental Eye Research
DOI 10.1016/j.exer.2004.09.017
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Abstract

Neutral lipid, including esterified cholesterol, and apolipoproteins B and E are abundant in basal deposits and drusen of aged and age-related maculopathy (ARM) eyes. The principal component of basal linear deposit (BlinD), a specific ARM lesion, is membranous debris, which if actually derived from membranes cannot account for extracellular neutral lipid. We therefore used a lipid-preserving ultrastructural method to obtain improved images of membranous debris. Maculas from 44 human donors (71-96 yr) were preserved <7.5 hr after death. Blocks were post-fixed in 2% osmium or osmium-tannic acid-paraphenylenediamine (OTAP) to preserve neutral lipid for thin-section transmission electron microscopic (TEM) examination. Solid particles identified by OTAP were considered closest to the in vivo state of extracellular lipids. Micrographs were examined for intermediate forms, with greatest weight given to comparable images from different preparations of same or fellow eyes. Twenty eyes of older adults (12 with ARM including fellows treated with photodynamic and radiation therapies) had adequately preserved extracellular lipid. The exterior surface of membranous debris was thicker and more electron-dense than basal infoldings of retinal pigment epithelium (RPE) cells. By OTAP, individual membranous debris profiles were solid (diameters, 80-200 nm) and formed tracks across or aggregations within basal laminar deposits. Solid particles and/or pools of neutral lipid were visible in BlinD and drusen. When processed to preserve lipid, membranous debris resembles neither membranes of surrounding cells nor vesicles possessing aqueous interiors but rather solid particles. These results are consistent with recent evidence implicating lipoprotein particles of intra-ocular origin as a potential source of neutral lipids, including esterified cholesterol, in the specific lesions of ARM.

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  • Drusen are focal deposits of proteins and neutral lipids such as esterified cholesterol, with apolipoproteins B and E located between the basal lamina of the RPE and the inner collagenous layer of BrM.

    “These are primarily termed drusen, focal deposits of proteins and neutral lipids such as esterified cholesterol, with apolipoproteins B and E located between the basal lamina of the RPE and the inner collagenous layer of BrM [65,66] (Figure 3).”

    From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [66]

  • Membranous structures accumulated within basal laminar deposits in Klc1−/− RPE appear to arise from the deposition of neutral lipids, like structures in postmortem AMD retinas.

    “Instead, they appear to arise from the deposition of neutral lipids, which, when preserved with the OTAP secondary fixative, appeared solid (Curcio et al., 2005), like the structures we observed in Klc1−/− RPE (Fig. 7 M), after using this preservation procedure (see Materials and methods).”

    From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Curcio et al., 2005

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Authors
Curcio, C. A., Presley, J. B., Millican, C. L., & Medeiros, N. E.
Affiliations
  • University of Alabama (US)
  • University of Alabama at Birmingham (US)
Corresponding author
Curcio, Christine A.
ORCID
Curcio, Christine A.
Venue
Experimental Eye Research
Publisher
Elsevier BV
Published
2005-06
Volume
80
Issue
6
Pages
761-775
ISSN
0014-4835 (ISSN-L)
DOI
10.1016/j.exer.2004.09.017
OpenAlex
W2094956499
Cited by
171
References
83
Citations by year
2026: 5 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 11 · 2018: 5 · 2017: 16 · 2016: 2 · 2015: 11 · 2014: 15 · 2013: 3 · 2012: 4
FWCI
10.05
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Eye Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Eye Institute (R01EY006109, EY06109)
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
age-related maculopathy, drusen, solid lipid particles, esterified cholesterol, apolipoprotein B, apolipoprotein E, retinal pigment epithelium, lipoprotein particles, lipid retention
MeSH terms
Aged, Aged, 80 and over, Female, Fluorescein Angiography, Humans, Hypertrophy, Lipids, Macular Degeneration, Male, Membranes, Microscopy, Electron, Pigment Epithelium of Eye, Retinal Drusen, Choroidal Neovascularization

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