Evidence map›Paper›PMID 21743013›Full record

ArticleInvestigative ophthalmology & visual science2011

Heparan sulfate regulates intraretinal axon pathfinding by retinal ganglion cells.

Minako Ogata-Iwao, Masaru Inatani, Keiichiro Iwao, Yuji Takihara, Yuko Nakaishi-Fukuchi, Fumitoshi Irie, Shigeru Sato, Takahisa Furukawa, Yu Yamaguchi, Hidenobu Tanihara

Open access · greenAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. The role of heparan sulphate in development: the ectodermal story.International journal of experimental pathology · 2016
    Review
  7. Article
  8. Macular optical coherence tomography in patients with unilateral optic nerve hypoplasia.Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus · 2015
    Article
  9. Article
  10. Role of heparan sulfate proteoglycans in optic disc and stalk morphogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2014
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. The glomerular basement membrane as a model system to study the bioactivity of heparan sulfate glycosaminoglycans.Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2012
    Review
  18. Article
  19. A roundabout way to cancer.Advances in cancer research · 2012
    Review
  20. 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

10 authors at 2 institutions in 2 countries.

Minako Ogata-IwaoDepartment of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Japan.
Masaru Inatani
Keiichiro Iwao
Yuji Takihara
Yuko Nakaishi-Fukuchi
Fumitoshi Irie
Shigeru Sato
Takahisa Furukawa
Yu Yamaguchi
Hidenobu Tanihara
Kumamoto University · JPSanford Burnham Prebys Medical Discovery Institute · US

Funding

Tissue CultureP01HD025938 · NICHD · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YAMAGUCHI, YU · 1989 to 2011
$13.6M
Heparan Sulfate in Skeletal Development and DiseasesR01AR055670 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YAMAGUCHI, YU · 2008 to 2018
$4.9M
NIAMS NIH HHS R01 AR055670NICHD NIH HHS P01 HD025938
6 · The paper itself

Abstract

PURPOSE. Heparan sulfate (HS) is abundantly expressed in the developing neural retina; however, its role in the intraretinal axon guidance of retinal ganglion cells (RGCs) remains unclear. In this study, the authors examined whether HS was essential for the axon guidance of RGCs toward the optic nerve head. METHODS. The authors conditionally ablated the gene encoding the exostosin-1 (Ext1) enzyme, using the dickkopf homolog 3 (Dkk3)-Cre transgene, which disrupted HS expression in the mouse retina during directed pathfinding by RGC axons toward the optic nerve head. In situ hybridization, immunohistochemistry, DiI tracing, binding assay, and retinal explant assays were performed to evaluate the phenotypes of the mutants and the roles of HS in intraretinal axon guidance. RESULTS. Despite no gross abnormality in RGC distribution, the mutant RGC axons exhibited severe intraretinal guidance errors, including optic nerve hypoplasia, ectopic axon penetration through the full thickness of the neural retina and into the subretinal space, and disturbance of the centrifugal projection of RGC axons toward the optic nerve head. These abnormal phenotypes shared similarities with the RGC axon misguidance caused by mutations of genes encoding Netrin-1 and Slit-1/2. Explant assays revealed that the mutant RGCs exhibited disturbed Netrin-1-dependent axon outgrowth and Slit-2-dependent repulsion. CONCLUSIONS. The present study demonstrated that RGC axon projection toward the optic nerve head requires the expression of HS in the neural retina, suggesting that HS in the retina functions as an essential modulator of Netrin-1 and Slit-mediated intraretinal RGC axon guidance.

Indexed as

AnimalsAxonsEnzyme-Linked Immunosorbent AssayExostosin 1Eye AbnormalitiesFemaleFluorescent Antibody Technique, IndirectHeparan SulfateImmunoenzyme TechniquesIn Situ HybridizationIntercellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, Mutant StrainsMice, TransgenicExostosin 1Heparan SulfateIntercellular Signaling Peptides and ProteinsN-AcetylglucosaminyltransferasesNerve Growth FactorsNerve Tissue ProteinsNetrin-1Ntn1 protein, mouseSlit1 protein, mouseSlit Homolog 2 ProteinTumor Suppressor Proteins

Identifiers

PMID21743013
PMCPMC3176022
OpenAlexW2022435799

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.