Evidence map›Paper›PMID 39461953›Full record

ArticleNPJ Regenerative medicine2024

Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration.

Gregory P Campbell, Dwarkesh Amin, Kristin Hsieh, George S Hussey, Anthony J St Leger, Jeffrey M Gross, Stephen F Badylak, Takaaki Kuwajima

Abstract read
In one paragraph

Article in NPJ Regenerative medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
  2. Review
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  6. Review
  7. 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

8 authors.

Gregory P CampbellDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.ORCID http://orcid.org/0000-0001-6005-9723
Dwarkesh AminDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
Kristin HsiehDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
George S HusseyDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, 15219, USA.ORCID http://orcid.org/0000-0001-5636-0994
Anthony J St LegerDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
Jeffrey M GrossDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
Stephen F BadylakMcGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Takaaki KuwajimaDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA. kuwajima@pitt.edu.ORCID http://orcid.org/0000-0002-8398-3131

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
Assessing how ocular surface nerves, immune cells, and epithelial cells communicate to encourage neuro-immune homeostasisU01EY034711 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Daniel H Kaplan, HARINDER SINGH · 2022 to 2026
$7.5M
Contribution of Sympathetic Nerves to Herpes Stromal KeratitisR01EY026891 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ANTHONY J ST LEGER · 2017 to 2026
$4.7M
Elucidating the Molecular Underpinnings of Endogenous RPE RegenerationR01EY029410 · NEI · UNIVERSITY OF TEXAS AT AUSTIN · PI Jeffrey Gross · 2019 to 2026
$2.4M
Alcon Foundation (Alcon Foundation Inc.) Alcon Research Institute Young Investigator AwardEye and Ear Foundation of Pittsburgh Research GrantNEI NIH HHS P30 EY008098NEI NIH HHS R01 EY026891NEI NIH HHS R01 EY029410NEI NIH HHS U01 EY034711U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY026891U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY029410U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) U01EY034711
6 · The paper itself

Abstract

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy.

Identifiers

PMID39461953
PMCPMC11513974

What OpenQuestion holds

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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.