Evidence map›Paper›PMID 27440998›Full record

ArticleMolecular vision2016

Tyrosine triple mutated AAV2-BDNF gene therapy in a rat model of transient IOP elevation.

Tsutomu Igarashi, Koichi Miyake, Maika Kobayashi, Shuhei Kameya, Chiaki Fujimoto, Kenji Nakamoto, Hisatomo Takahashi, Toru Igarashi, Noriko Miyake, Osamu Iijima and 4 more

Open access · greenAbstract read
In one paragraph

Article in Molecular vision, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
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  4. Article
  5. Article
  6. The Role of Axonal Transport in Glaucoma.International journal of molecular sciences · 2022
    Review
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  9. Article
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  13. Loss of Shp2 Rescues BDNF/TrkB Signaling and Contributes to Improved Retinal Ganglion Cell Neuroprotection.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  14. Article
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 2 institutions in 1 country.

Tsutomu IgarashiDepartment of Ophthalmology, Nippon Medical School, Tokyo, Japan; Department of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Koichi MiyakeDepartment of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Maika KobayashiDepartment of Ophthalmology, Nippon Medical School, Tokyo, Japan; Department of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Shuhei KameyaDepartment of Ophthalmology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
Chiaki FujimotoDepartment of Ophthalmology, Nippon Medical School, Tokyo, Japan.
Kenji NakamotoDepartment of Ophthalmology, Nippon Medical School, Tokyo, Japan.
Hisatomo TakahashiDepartment of Ophthalmology, Nippon Medical School, Tokyo, Japan.
Toru IgarashiDepartment of Pediatrics, Nippon Medical School, Tokyo, Japan.
Noriko MiyakeDepartment of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Osamu IijimaDepartment of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Yukihiko HiraiDepartment of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Takashi ShimadaDepartment of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Takashi OkadaDepartment of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.
Hiroshi TakahashiDepartment of Ophthalmology, Nippon Medical School, Tokyo, Japan.
Nippon Medical School · JPChiba Hokusou Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeWe examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF).

methodsThe tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer.

resultsIntravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were preserved after transient IOP elevation in eyes treated with tm-scAAV2-BDNF but not in the other I/R groups. Significantly reduced glial fibrillary acidic protein (GFAP) immunostaining after I/R injury in the rats that received tm-scAAV2-BDNF indicated reduced retinal stress, and electroretinogram (ERG) analysis confirmed preservation of retinal function in the tm-scAAV2-BDNF group.

conclusionsThese results demonstrate the feasibility and effectiveness of neuroprotective gene therapy using tm-scAAV2-BDNF to protect the inner retina from transiently high intraocular pressure. An in vivo gene therapeutic approach to the clinical management of retinal diseases in conditions such as glaucoma, retinal artery occlusion, hypertensive retinopathy, and diabetic retinopathy thus appears feasible.

Indexed as

Intraocular PressureAnimalsBrain-Derived Neurotrophic FactorCell CountDependovirusDisease Models, AnimalElectroretinographyGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsHumansMutationRats, Sprague-DawleyRetinaRetinal Ganglion CellsTransduction, GeneticTyrosineBrain-Derived Neurotrophic FactorGlial Fibrillary Acidic ProteinGreen Fluorescent ProteinsTyrosine

Identifiers

PMID27440998
PMCPMC4947967
OpenAlexW2494885835

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.