Evidence map›Paper›PMID 31613797›Full record

ArticleJCI insight2019

Rb1/Rbl1/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma.

Ran Wei, Xiang Ren, Hongyu Kong, Zhongping Lv, Yongjiang Chen, Yunjing Tang, Yujiao Wang, Lirong Xiao, Tao Yu, Sabiha Hacibekiroglu and 4 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 38% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

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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

14 authors at 3 institutions in 2 countries.

Ran WeiResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Xiang RenResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Hongyu KongResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Zhongping LvResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Yongjiang ChenLunenfeld-Tanenbaum Research Institute, Sinai Health System, and Departments of Ophthalmology and Visual Science, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Yunjing TangResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Yujiao WangResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Lirong XiaoResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Tao YuLunenfeld-Tanenbaum Research Institute, Sinai Health System, and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Sabiha HacibekirogluLunenfeld-Tanenbaum Research Institute, Sinai Health System, and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Chen LiangResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Andras NagyLunenfeld-Tanenbaum Research Institute, Sinai Health System, and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Rod BremnerLunenfeld-Tanenbaum Research Institute, Sinai Health System, and Departments of Ophthalmology and Visual Science, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Danian ChenResearch Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.
Lunenfeld-Tanenbaum Research Institute · CASichuan University · CNState Key Laboratory of Biotherapy

Funding

CIHR
6 · The paper itself

Abstract

Von Hippel-Lindau (Vhl) protein inhibits hypoxia-inducible factor (Hif), yet its deletion in murine retina does not cause the extensive angiogenesis expected with Hif induction. The mechanism is unclear. Here we show that retinoblastoma tumor suppressor (Rb1) constrains expression of Hif target genes in the Vhl-/- retina. Deleting Rb1 induced extensive retinal neovascularization and autophagic ablation of photoreceptors in the Vhl-/- retina. RNA-sequencing, ChIP, and reporter assays showed Rb1 recruitment to and repression of certain Hif target genes. Activating Rb1 by deleting cyclin D1 induced a partial defect in the retinal superficial vascular plexus. Unexpectedly, removing Vhl suppressed retinoblastoma formation in murine Rb1/Rbl1-deficient retina but generated subretinal vascular growths resembling retinal angiomatous proliferation (RAP) and retinal capillary hemangioblastoma (RCH). Most stromal cells in the RAP/RCH-like lesions were Sox9+, suggesting a Müller glia origin, and expressed Lgals3, a marker of human brain hemangioblastoma. Thus, the Rb family limit Hif target gene expression in the Vhl-/- retina, and removing this inhibitory signal generates new models for RAP and RCH.

Indexed as

HemangioblastomaRetinal NeovascularizationRetinoblastoma Binding ProteinsRetinoblastoma-Like Protein p107Von Hippel-Lindau Tumor Suppressor ProteinAnimalsCell ProliferationMiceMice, KnockoutRetinal VesselsRb1 protein, mouseRbl1 protein, mouseRetinoblastoma Binding ProteinsRetinoblastoma-Like Protein p107VHL protein, mouseVon Hippel-Lindau Tumor Suppressor ProteinAngiogenesisAutophagyMouse modelsOphthalmologyTumor suppressors

Identifiers

PMID31613797
PMCPMC6948866
OpenAlexW2980610466

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.