Evidence map›Paper›PMID 21266465›Full record

ArticleJournal of cell science2011

Mutation in the βA3/A1-crystallin gene impairs phagosome degradation in the retinal pigmented epithelium of the rat.

J Samuel Zigler, Cheng Zhang, Rhonda Grebe, Gitanjali Sehrawat, Laszlo Hackler, Souvonik Adhya, Stacey Hose, D Scott McLeod, Imran Bhutto, Walid Barbour and 6 more

Abstract read
In one paragraph

Article in Journal of cell science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

44 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Article
  3. Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
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  9. DARPP32, a target of hyperactive mTORC1 in the retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Article
  11. Article
  12. Article
  13. Involvement of Anoikis in Dissociated Optic Nerve Fiber Layer Appearance.International journal of molecular sciences · 2021
    Review
  14. MTOR-initiated metabolic switch and degeneration in the retinal pigment epithelium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  15. Review
  16. Review
  17. Article
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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

16 authors at 3 institutions in 1 country.

J Samuel ZiglerThe Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
Cheng Zhang
Rhonda Grebe
Gitanjali Sehrawat
Laszlo Hackler
Souvonik Adhya
Stacey Hose
D Scott McLeod
Imran Bhutto
Walid Barbour
Geetha Parthasarathy
Donald J Zack
Yuri Sergeev
Gerard A Lutty
James T Handa
Debasish Sinha
Johns Hopkins University · USJohns Hopkins Medicine · USNational Institutes of Health · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
Proteins From Hereditary Eye Diseases: In-silico and Experimental StudiesZIAEY000476 · NEI · NATIONAL EYE INSTITUTE · PI SERGEEV, YURI · 2009 to 2025
$16.8M
Inflammatory cells of choroid: a therapeutic target in AMD.R01EY016151 · NEI · JOHNS HOPKINS UNIVERSITY · PI EDWARDS, MALIA MICHELLE · 2006 to 2024
$8.0M
AGE-induced Phenotype of the Retinal Pigment EpitheliumR01EY014005 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2001 to 2015
$6.4M
Vasculogenesis and hyperoxia in the developing retina.R01EY009357 · NEI · JOHNS HOPKINS UNIVERSITY · PI LUTTY, GERARD ANTHONY · 1993 to 2014
$5.3M
A novel bA3/A1-crystallin gene mutation results in persistent fetal vasculatureR01EY019037 · NEI · JOHNS HOPKINS UNIVERSITY · PI SINHA, DEBASISH · 2008 to 2015
$4.1M
Nrf2 signaling and oxidative stress in Age-related macular degenerationR01EY019904 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2010 to 2016
$4.1M
A CRYSTALLIN MUTATION WITH ABNORMAL ASTROCYTES AND RETINAL VESSELSR01EY018636 · NEI · JOHNS HOPKINS UNIVERSITY · PI SINHA, DEBASISH · 2009 to 2010
$820k
Intramural NIH HHSNEI NIH HHS EY016151-5NEI NIH HHS EY01765NEI NIH HHS EY018636NEI NIH HHS EY019037NEI NIH HHS EY019037-SNEI NIH HHS EY09357NEI NIH HHS EY14005NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY009357NEI NIH HHS R01 EY014005NEI NIH HHS R01 EY016151NEI NIH HHS R01 EY018636NEI NIH HHS R01 EY019037NEI NIH HHS R01 EY019904
6 · The paper itself

Abstract

Phagocytosis of the shed outer segment discs of photoreceptors is a major function of the retinal pigmented epithelium (RPE). We demonstrate for the first time that βA3/A1-crystallin, a major structural protein of the ocular lens, is expressed in RPE cells. Further, by utilizing the Nuc1 rat, in which the βA3/A1-crystallin gene is mutated, we show that this protein is required by RPE cells for proper degradation of outer segment discs that have been internalized in phagosomes. We also demonstrate that in wild-type RPE, βA3/A1-crystallin is localized to the lysosomes. However, in the Nuc1 RPE, βA3/A1-crystallin fails to translocate to the lysosomes, perhaps because misfolding of the mutant protein masks sorting signals required for proper trafficking. The digestion of phagocytized outer segments requires a high level of lysosomal enzyme activity, and cathepsin D, the major enzyme responsible for proteolysis of the outer segments, is decreased in mutant RPE cells. Interestingly, our results also indicate a defect in the autophagy process in the Nuc1 RPE, which is probably also linked to impaired lysosomal function, because phagocytosis and autophagy might share common mechanisms in degradation of their targets. βA3/A1-crystallin is a novel lysosomal protein in RPE, essential for degradation of phagocytosed material.

Indexed as

MutationAnimalsCrystallinsPhagosomesRatsRats, Sprague-DawleyRetinal Pigment EpitheliumbetaA3-crystallin, ratCrystallins

Identifiers

PMID21266465
PMCPMC3031366
OpenAlexW1969321137

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.