Evidence map›Paper›PMID 30341011›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

Loss of Shp2 Rescues BDNF/TrkB Signaling and Contributes to Improved Retinal Ganglion Cell Neuroprotection.

Nitin Chitranshi, Yogita Dheer, Mehdi Mirzaei, Yunqi Wu, Ghasem H Salekdeh, Mojdeh Abbasi, Veer Gupta, Roshana Vander Wall, Yuyi You, Stuart L Graham and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
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  3. Retinoid X receptor agonist 9CDHRA mitigates retinal ganglion cell apoptosis and neuroinflammation in a mouse model of glaucoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  14. Neuroserpin gene therapy inhibits retinal ganglion cell apoptosis and promotes functional preservation in glaucoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
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  17. Review
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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

11 authors at 4 institutions in 1 country.

Nitin ChitranshiFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia. Electronic address: nitin.chitranshi@mq.edu.au.
Yogita DheerFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia.
Mehdi MirzaeiFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia; Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia; Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia.
Yunqi WuFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia.
Ghasem H SalekdehDepartment of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Mojdeh AbbasiFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia.
Veer GuptaSchool of Medicine, Deakin University, Geelong, VIC, Australia.
Roshana Vander WallFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia.
Yuyi YouSave Sight Institute, Sydney University, Sydney, NSW, Australia.
Stuart L GrahamFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia; Save Sight Institute, Sydney University, Sydney, NSW, Australia.
Vivek GuptaFaculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia. Electronic address: vivek.gupta@mq.edu.au.
Macquarie University · AUDeakin University · AUThe University of Sydney · AUAGRF Ltd · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glaucoma is characterized by the loss of retinal ganglion cells (RGC), and accordingly the preservation of RGCs and their axons has recently attracted significant attention to improve therapeutic outcomes in the disease. Here, we report that Src homology region 2-containing protein tyrosine phosphatase 2 (Shp2) undergoes activation in the RGCs, in animal model of glaucoma as well as in the human glaucoma tissues and that Shp2 dephosphorylates tropomyosin receptor kinase B (TrkB) receptor, leading to reduced BDNF/TrkB neuroprotective survival signaling. This was elucidated by specifically modulating Shp2 expression in the RGCs in vivo, using adeno-associated virus serotype 2 (AAV2) constructs. Shp2 upregulation promoted endoplasmic reticulum (ER) stress and apoptosis, along with functional and structural deficits in the inner retina. In contrast, loss of Shp2 decelerated the loss of RGCs, preserved their function, and suppressed ER stress and apoptosis in glaucoma. This report constitutes the first identification of Shp2-mediated TrkB regulatory mechanisms in the RGCs that can become a potential therapeutic target in both glaucoma and other neurodegenerative disorders.

Indexed as

AnimalsBlotting, WesternBrain-Derived Neurotrophic FactorDisease Models, AnimalElectrophoresis, Polyacrylamide GelElectroretinographyGlaucomaMaleProtein Tyrosine Phosphatase, Non-Receptor Type 11RatsRats, Sprague-DawleyReceptor, trkBRetinaRetinal Ganglion CellsSignal TransductionBrain-Derived Neurotrophic FactorNtrk2 protein, ratProtein Tyrosine Phosphatase, Non-Receptor Type 11Ptpn11 protein, ratReceptor, trkBAAV2apoptosisBDNF/TrkBER stressgene deliveryglaucomaretinaRGCsShp2

Identifiers

PMID30341011
PMCPMC6369445
OpenAlexW2894870824

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.