Evidence map›Paper›PMID 22503691›Full record

ReviewMolecular aspects of medicine2012

How does the macula protect itself from oxidative stress?

James T Handa

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Molecular aspects of medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% 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

95 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Clinical anatomy of the macula.Medical hypothesis, discovery & innovation ophthalmology journal · 2025
    Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Glycative stress as a cause of macular degeneration.Progress in retinal and eye research · 2024
    Review
  20. Article

35 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

1 author at 1 institution in 1 country.

James T HandaWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. jthanda@jhmi.edu
Johns Hopkins University · US

Funding

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 R01 EY014005NEI NIH HHS R01 EY019904
6 · The paper itself

Abstract

Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD.

Indexed as

Oxidative StressAgingAnimalsDisease Models, AnimalEpitopesHumansImmunity, InnateMacula LuteaMacular DegenerationMiceNF-E2-Related Factor 2Oxidation-ReductionReactive Oxygen SpeciesRisk FactorsSignal TransductionEpitopesNF-E2-Related Factor 2Reactive Oxygen Species

Identifiers

PMID22503691
PMCPMC3392444
OpenAlexW2039002855

What OpenQuestion holds

Textmetadata
LicenceTDM
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.