Evidence map›Paper›PMID 31078532›Full record

ArticleAmerican journal of ophthalmology2019

The Role of FGF9 in the Production of Neural Retina and RPE in a Pluripotent Stem Cell Model of Early Human Retinal Development.

David M Gamm, Eric Clark, Elizabeth E Capowski, Ruchira Singh

Abstract read
In one paragraph

Article in American journal of ophthalmology, 2019. 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
1.3field-weighted citation impact, top 20% 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, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 ocular retardation J mice.Developmental dynamics : an official publication of the American Association of Anatomists · 2023
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Pluripotent Stem Cell-Based Organoid Technologies for Developing Next-Generation Vision Restoration Therapies of Blindness.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2021
    Review
  14. Article
  15. Retinal organoids: a window into human retinal development.Development (Cambridge, England) · 2020
    Review
  16. Review
  17. Review
  18. Article
  19. The Spectrum ofGenes · 2019
    Review
  20. The Prospects for Retinal Organoids in Treatment of Retinal Diseases.Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)
    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 3 institutions in 1 country.

David M GammMcPherson Eye Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, USA; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address: dgamm@wics.edu.
Eric ClarkDepartment of Cell Biology, Neurobiology, & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Elizabeth E CapowskiWaisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Ruchira SinghDepartment of Ophthalmology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York, USA.
University of Wisconsin–Madison · USMedical College of Wisconsin · USUniversity of Rochester Medical Center · US

Funding

Mechanisms of Retinogenesis in Human Stem CellsR01EY021218 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI GAMM, DAVID M · 2010 to 2017
$2.2M
NEI NIH HHS R01 EY021218
6 · The paper itself

Abstract

purposeTo investigate the role of fibroblast growth factors (FGFs) in the production of neural retina (NR) and retinal pigmented epithelium (RPE) in a human pluripotent stem cell model of early retinal development.

methodsHuman induced pluripotent stem cell (hiPSC) lines from an individual with microphthalmia caused by a functional null mutation (R200Q) in visual system homeobox 2 (VSX2), a transcription factor involved in early NR progenitor cell (NRPC) production, and a normal sibling were differentiated along the retinal and forebrain lineages using an established protocol. Quantitative and global gene expression analyses (microarray and RNAseq) were used to investigate endogenous FGF expression profiles in these cultures over time. Based on these results, mutant and control hiPSC cultures were treated exogenously with selected FGFs and subjected to gene and protein expression analyses to determine their effects on RPE and NR production.

resultsWe found that FGF9 and FGF19 were selectively increased in early hiPSC-derived optic vesicles (OVs) when compared to isogenic cultures of hiPSC-derived forebrain neurospheres. Furthermore, these same FGFs were downregulated over time in (R200Q)VSX2 hiPSC-OVs relative to sibling control hiPSC-OVs. Interestingly, long-term supplementation with FGF9, but not FGF19, partially rescued the mutant retinal phenotype of the (R200Q)VSX2 hiPSC-OV model. However, antagonizing FGF9 in wild-type control hiPSCs did not alter OV development.

conclusionsOur results show that FGF9 acts in concert with VSX2 to promote NR differentiation in hiPSC-OVs and has potential to be used to manipulate early retinogenesis and mitigate ocular defects caused by functional loss of VSX2 activity. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Indexed as

Gene Expression Regulation, DevelopmentalBlotting, WesternCell DifferentiationCells, CulturedFibroblast Growth Factor 9HumansImmunohistochemistryInduced Pluripotent Stem CellsMicrophthalmosPhenotypeRetinal Pigment EpitheliumRNAFGF9 protein, humanFibroblast Growth Factor 9RNA

Identifiers

PMID31078532
PMCPMC6842420
OpenAlexW2944061802

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.