Evidence map›Paper›PMID 25758814›Full record

ArticleInvestigative ophthalmology & visual science2015

Lipofuscin redistribution and loss accompanied by cytoskeletal stress in retinal pigment epithelium of eyes with age-related macular degeneration.

Thomas Ach, Elen Tolstik, Jeffrey D Messinger, Anna V Zarubina, Rainer Heintzmann, Christine A Curcio

Open access · hybridAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed
15.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

110 citing papers in PubMed, 174 citations in OpenAlex.

  1. Trial
  2. Impaired Rod-Mediated Vision is the Functional Hallmark of Ageing and Early and Intermediate Age-Related Macular Degeneration.Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Observational
  10. Review
  11. Review
  12. Article
  13. Article
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  15. Extensive macular atrophy with pseudodrusen-like appearance: comprehensive review of the literature.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024
    Review
  16. Article
  17. Multispectral label-freeJournal of biomedical optics · 2024
    Article
  18. Review
  19. Age-Related Macular Degeneration, a Mathematically Tractable Disease.Investigative ophthalmology & visual science · 2024
    Review
  20. Article

50 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 3 countries.

Thomas AchUniversity of Alabama at Birmingham Department of Ophthalmology, Birmingham, Alabama, United States 2University Hospital Würzburg, Department of Ophthalmology, Würzburg, Germany.
Elen TolstikLeibniz Institute of Photonic Technology, Jena, Germany 5King's College London, Randall Division of Cell & Molecular Biophysics, London, United Kingdom.
Jeffrey D MessingerUniversity of Alabama at Birmingham Department of Ophthalmology, Birmingham, Alabama, United States.
Anna V ZarubinaUniversity of Alabama at Birmingham Department of Ophthalmology, Birmingham, Alabama, United States.
Rainer HeintzmannLeibniz Institute of Photonic Technology, Jena, Germany 5King's College London, Randall Division of Cell & Molecular Biophysics, London, United Kingdom.
Christine A CurcioUniversity of Alabama at Birmingham Department of Ophthalmology, Birmingham, Alabama, United States.
University of Alabama at Birmingham · USKing's College London · GBLeibniz Institute of Photonic Technology · DE

Funding

Validated Autofluorescence in Age-Related Macular DegenerationR01EY015520 · NEI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SMITH, ROLAND THEODORE · 2005 to 2018
$6.0M
QUANTITATIVE ANAYLSIS OF AGING RETINAR01EY006109 · NEI · UNIVERSITY OF WASHINGTON · PI CURCIO, CHRISTINE A · 1986 to 2012
$3.5M
NEI NIH HHS R01 EY006109NEI NIH HHS R01 EY015520NEI NIH HHS R01 EY06109
6 · The paper itself

Abstract

purposeLipofuscin (LF) and melanolipofuscin (MLF) of the retinal pigment epithelium (RPE) are the principal sources of autofluorescence (AF) signals in clinical fundus-AF imaging. Few details about the subcellular distribution of AF organelles in AMD are available. We describe the impact of aging and AMD on RPE morphology revealed by the distribution of AF LF/MLF granules and actin cytoskeleton in human tissues.

methodsThirty-five RPE-Bruch's membrane flatmounts from 35 donors were prepared (postmortem: ≤4 hours). Ex vivo fundus examination at the time of accession revealed either absence of chorioretinal pathologies (10 tissues; mean age: 83.0 ± 2.6 years) or stages of AMD (25 tissues; 85.0 ± 5.8 years): early AMD, geographic atrophy, and late exudative AMD. Retinal pigment epithelium cytoskeleton was labeled with AlexaFluor647-Phalloidin. Tissues were imaged on a spinning-disk fluorescence microscope and a high-resolution structured illumination microscope.

resultsAge-related macular degeneration impacts individual RPE cells by (1) lipofuscin redistribution by (i) degranulation (granule-by-granule loss) and/or (ii) aggregation and apparent shedding into the extracellular space; (2) enlarged RPE cell area and conversion from convex to irregular and sometimes concave polygons; and (3) cytoskeleton derangement including separations and breaks around subretinal deposits, thickening, and stress fibers.

conclusionsWe report an extensive and systematic en face analysis of LF/MLF-AF in AMD eyes. Redistribution and loss of AF granules are among the earliest AMD changes and could reduce fundus AF signal attributable to RPE at these locations. Data can enhance the interpretation of clinical fundus-AF and provide a basis for future quantitative studies.

Indexed as

AgedAged, 80 and overAgingBruch MembraneCytoskeletonFemaleHumansLipofuscinMacular DegenerationMicroscopy, ConfocalRetinal Pigment EpitheliumRetinal PigmentsSpectrometry, FluorescenceLipofuscinRetinal Pigments

Identifiers

PMID25758814
PMCPMC4455310
OpenAlexW2334245029

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.