Evidence map›Paper›PMID 29204649›Full record

ArticleInvestigative ophthalmology & visual science2017

AAV2-Mediated Transduction of the Mouse Retina After Optic Nerve Injury.

Robert W Nickells, Heather M Schmitt, Margaret E Maes, Cassandra L Schlamp

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Glaucomatous retinal ganglion cells: death and protection.International journal of ophthalmology · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. BCLXCell death & disease · 2021
    Article
  13. Article
  14. Mitochondrial Transfer of the Mutant HumanTranslational vision science & technology · 2020
    Article
  15. Article
  16. Mouse γ-Synuclein Promoter-Mediated Gene Expression and Editing in Mammalian Retinal Ganglion Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  17. Article
  18. Article
  19. Article
  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

4 authors at 2 institutions in 2 countries.

Robert W NickellsDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States.
Heather M SchmittDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States.
Margaret E MaesDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States.
Cassandra L SchlampDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States.
University of Wisconsin–Madison · USInstitute of Science and Technology Austria · AT

Funding

UW Vision Research Core - Administrative CoreP30EY016665 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI Donna M Peters · 2005 to 2026
$12.6M
The molecular mechanism of retinal ganglion cell deathR01EY012223 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI NICKELLS, ROBERT W · 2005 to 2017
$6.3M
Graduate Training In Cellular And Molecular Pathogenesis Of Human DiseasesT32GM081061 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FABRY, ZSUZSANNA · 2010 to 2019
$1.8M
NEI NIH HHS P30 EY016665NEI NIH HHS R01 EY012223NIGMS NIH HHS T32 GM081061
6 · The paper itself

Abstract

Purpose: Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful therapeutic for the rescue and regeneration of these cells after optic nerve damage. However, early after damage, RGCs undergo atrophic changes, including gene silencing. It is not known if these changes will deleteriously affect transduction and transgene expression, or if the therapeutic protein can influence reactivation of the endogenous genome. Methods: Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the proapoptotic Bax gene were reared. The Bax mutant blocks apoptosis, but RGCs still exhibit nuclear atrophy and gene silencing. At times ranging from 1 hour to 4 weeks after optic nerve crush (ONC), eyes received an intravitreal injection of AAV2 virus carrying the Cre recombinase. Successful transduction was monitored by expression of the tdTomato reporter. Immunostaining was used to localize tdTomato expression in select cell types. Results: Successful transduction of RGCs was achieved at all time points after ONC using AAV2 expressing Cre from the phosphoglycerate kinase (Pgk) promoter, but not the CMV promoter. ONC promoted an increase in the transduction of cell types in the inner nuclear layer, including Müller cells and rod bipolar neurons. There was minimal evidence of transduction of amacrine cells and astrocytes in the inner retina or optic nerve. Conclusions: Damaged RGCs can be transduced and at least some endogenous genes can be subsequently activated. Optic nerve damage may change retinal architecture to allow greater penetration of an AAV2 virus to transduce several additional cell types in the inner nuclear layer.

Indexed as

Gene Expression RegulationAnimalsDisease Models, AnimalGenetic TherapyGenetic VectorsMiceMice, TransgenicMicroscopy, Electron, TransmissionOptic NerveOptic Nerve InjuriesReceptors, Cell SurfaceRetinal Ganglion CellsRNATransduction, GeneticKIAA0319L protein, mouseReceptors, Cell SurfaceRNA

Identifiers

PMID29204649
PMCPMC5716181
OpenAlexW2773068071

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.