Evidence map›Paper›PMID 33960384›Full record

ArticleDevelopment (Cambridge, England)2021

Environmental oxygen regulates astrocyte proliferation to guide angiogenesis during retinal development.

Robin M Perelli, Matthew L O'Sullivan, Samantha Zarnick, Jeremy N Kay

Open access · hybridAbstract read
In one paragraph

Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Development of Retinal Astroglia.Annual review of vision science · 2025
    Review
  8. Targeting adenosine APurinergic signalling · 2025
    Review
  9. Ref-1 redox activity regulates retinal neovascularization by modulating transcriptional activation of HIF-1α.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. The Vasculature in Pulmonary Fibrosis.Current tissue microenvironment reports · 2022
    Article
  19. Article
  20. Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021
    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

4 authors at 1 institution in 1 country.

Robin M PerelliDepartment of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
Matthew L O'SullivanDepartment of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA.
Samantha ZarnickDepartment of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
Jeremy N KayDepartment of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0001-6145-1604
Duke University · US

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
Mechanisms of naturally-occurring astrocyte death during retinal developmentR01EY030611 · NEI · DUKE UNIVERSITY · PI Jeremy N Kay · 2019 to 2026
$2.7M
NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY030611
6 · The paper itself

Abstract

Angiogenesis in the developing mammalian retina requires patterning cues from astrocytes. Developmental disorders of retinal vasculature, such as retinopathy of prematurity (ROP), involve arrest or mispatterning of angiogenesis. Whether these vascular pathologies involve astrocyte dysfunction remains untested. Here, we demonstrate that the major risk factor for ROP - transient neonatal exposure to excess oxygen - disrupts formation of the angiogenic astrocyte template. Exposing newborn mice to elevated oxygen (75%) suppressed astrocyte proliferation, whereas return to room air (21% oxygen) at postnatal day 4 triggered extensive proliferation, massively increasing astrocyte numbers and disturbing their spatial patterning prior to the arrival of developing vasculature. Proliferation required astrocytic HIF2α and was also stimulated by direct hypoxia (10% oxygen), suggesting that astrocyte oxygen sensing regulates the number of astrocytes produced during development. Along with astrocyte defects, return to room air also caused vascular defects reminiscent of ROP. Strikingly, these vascular phenotypes were more severe in animals that had larger numbers of excess astrocytes. Together, our findings suggest that fluctuations in environmental oxygen dysregulate molecular pathways controlling astrocyte proliferation, thereby generating excess astrocytes that interfere with retinal angiogenesis.

Indexed as

AnimalsAnimals, NewbornAstrocytesCell ProliferationFemaleHypoxiaMiceNeovascularization, PathologicNeovascularization, PhysiologicOxygenRetinaRetinal VesselsRetinopathy of PrematurityOxygenAstrocyteDevelopmentHypoxiaMouseOxygen-induced retinopathyRetinaRetinopathy of prematurity

Identifiers

PMID33960384
PMCPMC8126409
OpenAlexW3157722161

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.