Evidence map›Paper›PMID 27654416›Full record

ArticleInvestigative ophthalmology & visual science2016

Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy.

Maria Vähätupa, Stuart Prince, Suvi Vataja, Teija Mertimo, Marko Kataja, Kati Kinnunen, Varpu Marjomäki, Hannu Uusitalo, Masanobu Komatsu, Tero A H Järvinen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
4.6field-weighted citation impact, top 6% 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

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Article
  7. Article
  8. Proteomics Analysis of R-Ras Deficiency in Oxygen Induced Retinopathy.International journal of molecular sciences · 2023
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Retinal Vasculature in Development and Diseases.Annual review of vision science · 2018
    Review
  19. Prolonged activation of cAMP signaling leads to endothelial barrier disruption via transcriptional repression of RRAS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018
    Article
  20. Animal models of ocular angiogenesis: from development to pathologies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 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

11 authors at 6 institutions in 2 countries.

Maria VähätupaDepartment of Ophthalmology, University of Tampere, Tampere, Finland 2Department of Anatomy, University of Tampere, Tampere, Finland.
Stuart PrinceDepartment of Anatomy, University of Tampere, Tampere, Finland.
Suvi VatajaDepartment of Ophthalmology, University of Tampere, Tampere, Finland.
Teija MertimoDepartment of Ophthalmology, University of Tampere, Tampere, Finland.
Marko KatajaEye Centre, Tampere University Hospital, Tampere, Finland.
Kati KinnunenDepartment of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
Varpu MarjomäkiDepartment of Biological and Environmental Science/Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland.
Hannu UusitaloDepartment of Ophthalmology, University of Tampere, Tampere, Finland 3Eye Centre, Tampere University Hospital, Tampere, Finland.
Masanobu KomatsuSanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida, United States.
Tero A H JärvinenDepartment of Anatomy, University of Tampere, Tampere, Finland 7Department of Musculoskeletal Disorders, Tampere University Hospital, Tampere, Finland.
Hannele Uusitalo-JärvinenDepartment of Ophthalmology, University of Tampere, Tampere, Finland 3Eye Centre, Tampere University Hospital, Tampere, Finland.
Tampere University · FITampere University · FIKuopio University Hospital · FISanford Burnham Prebys Medical Discovery Institute · USTampere University Hospital · FIUniversity of Jyväskylä · FI

Funding

Normalization of tumor vasculature by R-RasR01CA125255 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI KOMATSU, MASANOBU · 2008 to 2018
$4.2M
NCI NIH HHS R01 CA125255
6 · The paper itself

Abstract

purposeThe role of R-Ras in retinal angiogenesis and vascular permeability was evaluated in an oxygen-induced retinopathy (OIR) model using R-Ras knockout (KO) mice and in human diabetic neovascular membranes.

methodsMice deficient for R-Ras and their wild-type (WT) littermates were subjected to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to room air. At P17 retinal vascularization was examined from whole mounts, and retinal vascular permeability was studied using Miles assay. Real-time RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of R-Ras in retina during development or in the OIR model. The degree of pericyte coverage and vascular endothelial (VE)-cadherin expression on WT and R-Ras KO retinal blood vessels was quantified using confocal microscopy. The correlation of R-Ras with vascular endothelial growth factor receptor 2 (VEGFR2) and human serum albumin on human proliferative diabetic retinopathy membranes was assessed using immunohistochemistry.

resultsIn retina, R-Ras expression was mostly restricted to the vasculature. Retinal vessels in the R-Ras KO mice were significantly more permeable than WT controls in the OIR model. A significant reduction in the direct physical contact between pericytes and blood vessel endothelium as well as reduced VE-cadherin immunostaining was found in R-Ras-deficient mice. In human proliferative diabetic retinopathy neovascular membranes, R-Ras expression negatively correlated with increased vascular leakage and expression of VEGFR2, a marker of blood vessel immaturity.

conclusionsOur results suggest that R-Ras has a role in controlling retinal vessel maturation and stabilization in ischemic retinopathy and provides a potential target for pharmacologic manipulation to treat diabetic retinopathy.

Identifiers

PMID27654416
PMCPMC5032915
OpenAlexW2521411735

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.