Evidence map›Paper›PMID 27052802›Full record

ArticleGene therapy2016

Reduced retinal transduction and enhanced transgene-directed immunogenicity with intravitreal delivery of rAAV following posterior vitrectomy in dogs.

R F Boyd, S L Boye, T J Conlon, K E Erger, D G Sledge, I M Langohr, W W Hauswirth, A M Komáromy, S E Boye, S M Petersen-Jones and 1 more

Open access · bronzeAbstract readComment
In one paragraph

Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  4. Article
  5. Article
  6. Pig Models in Retinal Research and Retinal Disease.Cold Spring Harbor perspectives in medicine · 2024
    Review
  7. Article
  8. AAV2-antiVEGFscFv gene therapy for retinal neovascularization.Molecular therapy. Methods & clinical development · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. From Bench to Bed: The Current Genome Editing Therapies for Glaucoma.Frontiers in cell and developmental biology · 2022
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Assessing retinal ganglion cell damage.Eye (London, England) · 2017
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

R F BoydDepartment of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA.
S L BoyeDepartment of Ophthalmology, University of Florida College of Medicine, Gainesville, FL, USA.
T J ConlonDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
K E ErgerDepartment of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
D G SledgeDiagnostic Center for Population and Animal Health, Michigan State University, East Lansing, MI, USA.
I M LangohrDiagnostic Center for Population and Animal Health, Michigan State University, East Lansing, MI, USA.
W W HauswirthDepartment of Ophthalmology, University of Florida College of Medicine, Gainesville, FL, USA.
A M KomáromyDepartment of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA.
S E BoyeDepartment of Ophthalmology, University of Florida College of Medicine, Gainesville, FL, USA.
S M Petersen-JonesDepartment of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA.
J T BartoeDepartment of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA.
Michigan State University · USUniversity of Florida · USFlorida College · US

Funding

Translational Research for Retinal Degeneration TherapiesR01EY017549 · NEI · UNIVERSITY OF PENNSYLVANIA · PI BELTRAN, WILLIAM A. · 2007 to 2024
$14.1M
rAAV-CNGB3 Gene Therapy for Achromatopsia: Translational Research StudiesR24EY022023 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2013 to 2017
$7.9M
Translational Gene Therapy for Rhodopsin Autosomal Dominant Retinitis PigmentosaR24EY022012 · NEI · UNIVERSITY OF PENNSYLVANIA · PI AGUIRRE, GUSTAVO DAVID · 2012 to 2016
$7.9M
Engineering AAV for safe and efficient gene delivery to the human retinaR01EY024280 · NEI · UNIVERSITY OF FLORIDA · PI Shannon Elizabeth Boye · 2014 to 2026
$7.5M
Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Achromatopsia - Disease Mechanisms and Cone-Directed Gene TherapyR01EY019304 · NEI · UNIVERSITY OF PENNSYLVANIA · PI KOMAROMY, ANDRAS · 2009 to 2013
$2.3M
NEI NIH HHS P30 EY021721NEI NIH HHS R01 EY017549NEI NIH HHS R01 EY019304NEI NIH HHS R01 EY024280NEI NIH HHS R24 EY022012NEI NIH HHS R24 EY022023
6 · The paper itself

Abstract

Adeno-associated virus (AAV) vector-based gene therapy is a promising treatment strategy for delivery of neurotrophic transgenes to retinal ganglion cells (RGCs) in glaucoma patients. Retinal distribution of transgene expression following intravitreal injection (IVT) of AAV is variable in animal models and the vitreous humor may represent a barrier to initial vector penetration. The primary goal of our study was to investigate the effect of prior core vitrectomy with posterior hyaloid membrane peeling on pattern and efficiency of transduction of a capsid amino acid substituted AAV2 vector, carrying the green fluorescent protein (GFP) reporter transgene following IVT in dogs. When progressive intraocular inflammation developed starting 4 weeks post IVT, the study plan was modified to allow detailed characterization of the etiology as a secondary goal. Unexpectedly, surgical vitrectomy was found to significantly limit transduction, whereas in non-vitrectomized eyes transduction efficiency reached upwards to 37.3% of RGC layer cells. The developing retinitis was characterized by mononuclear cell infiltrates resulting from a delayed-type hypersensitivity reaction, which we suspect was directed at the GFP transgene. Our results, in a canine large animal model, support caution when considering surgical vitrectomy before IVT for retinal gene therapy in patients, as prior vitrectomy appears to significantly reduce transduction efficiency and may predispose the patient to development of vector-induced immune reactions.

Indexed as

VitrectomyAnimalsDependovirusDogsGenetic VectorsGreen Fluorescent ProteinsHumansRetinaTransduction, GeneticTransgenesGreen Fluorescent Proteins

Identifiers

PMID27052802
PMCPMC4891289
OpenAlexW2332857514

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.