Evidence map›Paper›PMID 26538774›Full record

ArticleTransactions of the American Ophthalmological Society2015

Lipoprotein(A) with An Intact Lysine Binding Site Protects the Retina From an Age-Related Macular Degeneration Phenotype in Mice (An American Ophthalmological Society Thesis).

James T Handa, Mizuki Tagami, Katayoon Ebrahimi, Gregor Leibundgut, Anna Janiak, Joseph L Witztum, Sotirios Tsimikas

Open access · greenAbstract read
In one paragraph

Article in Transactions of the American Ophthalmological Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. The roles of glycerophospholipids in the aging retina and age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Lipids as Regulators of Cellular Senescence.Frontiers in physiology · 2022
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related Macular Degeneration.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017
    Review
  13. Lipoprotein (a): a historical appraisal.Journal of lipid research · 2017
    Review
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

7 authors at 3 institutions in 1 country.

James T HandaWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
Mizuki TagamiWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
Katayoon EbrahimiWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
Gregor LeibundgutDepartment of Medicine, University of California at San Diego, La Jolla, California.
Anna JaniakWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
Joseph L WitztumDepartment of Medicine, University of California at San Diego, La Jolla, California.
Sotirios TsimikasDepartment of Medicine, University of California at San Diego, La Jolla, California.
University of California, San Diego · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4M
Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
AGE-induced Phenotype of the Retinal Pigment EpitheliumR01EY014005 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2001 to 2015
$6.4M
Nrf2 signaling and oxidative stress in Age-related macular degenerationR01EY019904 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2010 to 2016
$4.1M
NEI NIH HHS EY019904NEI NIH HHS EY14005NEI NIH HHS P30 EY001765NEI NIH HHS P30EY001765NEI NIH HHS R01 EY014005NEI NIH HHS R01 EY019904NHLBI NIH HHS HL 088093
6 · The paper itself

Abstract

purposeTo test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB).

methodsHuman maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. "Wild-type Lp(a)" mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and "mutant LBS(-) Lp(a)" mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid-containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids.

resultsOxidized phospholipids, apo(a), and apoB accumulate in maculas, including drusen, of age-related macular degeneration (AMD) samples and age-matched controls. Lp(a) mice fed a high-fat diet developed age-related changes. However, mutant LBS(-) Lp(a) mice fed a high-fat diet developed retinal pigment epithelial cell degeneration and drusen. These changes were associated with increased OxPL, decreased antioxidant defenses, increased complement, and decreased complement regulators.

conclusionsHuman maculas accumulate Lp(a) and OxPL. Mutant LBS(-) Lp(a) mice, lacking the ability to bind E06-detectable oxidized phospholipid, develop AMD-like changes. The ability of Lp(a) to bind E06-detectable OxPL may play a protective role in AMD.

Indexed as

AdultAgedAged, 80 and overAnimalsApolipoproteins AApolipoproteins BBinding SitesDisease Models, AnimalFemaleHumansImmunohistochemistryLipoprotein(a)LysineMacula LuteaMacular DegenerationMaleApolipoproteins AApolipoproteins BLipoprotein(a)LysinePhospholipids

Identifiers

PMID26538774
PMCPMC4601905
OpenAlexW2470227068

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.