Evidence map›Paper›PMID 26775053›Full record

ArticleExperimental eye research2016

Subretinal AAV2.COMP-Ang1 suppresses choroidal neovascularization and vascular endothelial growth factor in a murine model of age-related macular degeneration.

Nathan G Lambert, Xiaohui Zhang, Ruju R Rai, Hironori Uehara, Susie Choi, Lara S Carroll, Subrata K Das, Judd M Cahoon, Brian H Kirk, Blaine M Bentley and 1 more

Open access · greenAbstract read
In one paragraph

Article in Experimental eye research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. New Therapies of Neovascular AMD-Beyond Anti-VEGFs.Vision (Basel, Switzerland) · 2018
    Review
  9. Article
  10. Retinal and choroidal angiogenesis: a review of new targets.International journal of retina and vitreous · 2017
    Review
  11. Article
  12. Review
  13. 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

11 authors at 1 institution in 1 country.

Nathan G LambertAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA.
Xiaohui ZhangAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA.
Ruju R RaiAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA.
Hironori UeharaAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA.
Susie ChoiAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA.
Lara S CarrollAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA.
Subrata K DasAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA.
Judd M CahoonAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA.
Brian H KirkAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA.
Blaine M BentleyAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA.
Balamurali K AmbatiAmbati Lab, John A. Moran Eye Center, Salt Lake City, UT, USA; Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA. Electronic address: bala.ambati@utah.edu.
University of Utah · US

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
Intraceptor Interference of VEGF PathwaysR01EY017182 · NEI · UNIVERSITY OF UTAH · PI AMBATI, BALAMURALI K · 2007 to 2017
$3.6M
COMP-ANG1: VASCULAR NORMALIZATION AND NEUROPROTECTION FOR DIABETIC RETINOPATHYR01EY026029 · NEI · UNIVERSITY OF UTAH · PI AMBATI, BALAMURALI K · 2016 to 2019
$1.3M
NEI NIH HHS R01 EY017182NEI NIH HHS R01 EY026029NIDDK NIH HHS P30 DK020579
6 · The paper itself

Abstract

To assess whether Tie2-mediated vascular stabilization ameliorates neovascular age-related macular degeneration (AMD), we investigated the impact of adeno-associated virus-mediated gene therapy with cartilage oligomeric matrix protein angiopoietin-1 (AAV2.COMP-Ang1) on choroidal neovascularization (CNV), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF) in a mouse model of the disease. We treated mice with subretinal injections of AAV2.COMP-Ang1 or control (AAV2.AcGFP, AAV2.LacZ, and phosphate-buffered saline). Subretinal AAV2 localization and plasmid protein expression was verified in the retinal pigment epithelium (RPE)/choroid of mice treated with all AAV2 constructs. Laser-assisted simulation of neovascular AMD was performed and followed by quantification of HIF, VEGF, and CNV in each experimental group. We found that AAV2.COMP-Ang1 was associated with a significant reduction in VEGF levels (29-33%, p < 0.01) and CNV volume (60-70%, p < 0.01), without a concomitant decrease in HIF1-α, compared to all controls. We concluded that a) AAV2 is a viable vector for delivering COMP-Ang1 to subretinal tissues, b) subretinal COMP-Ang1 holds promise as a prospective treatment for neovascular AMD, and c) although VEGF suppression in the RPE/choroid may be one mechanism by which AAV2.COMP-Ang1 reduces CNV, this therapeutic effect may be hypoxia-independent. Taken together, these findings suggest that AAV2.COMP-Ang1 has potential to serve as an alternative or complementary option to anti-VEGF agents for the long-term amelioration of neovascular AMD.

Indexed as

Angiopoietin-1AnimalsBlotting, WesternCartilage Oligomeric Matrix ProteinChoroidal NeovascularizationDependovirusDisease Models, AnimalGenetic TherapyGenetic VectorsHypoxia-Inducible Factor 1Macular DegenerationMaleMiceMice, Inbred C57BLRetinal Pigment EpitheliumVascular Endothelial Growth Factor AAngiopoietin-1Cartilage Oligomeric Matrix ProteinHypoxia-Inducible Factor 1TSP5 protein, humanVascular Endothelial Growth Factor AAdeno-associated virusAge-related macular degenerationAngiopoietin-1Cartilage oligomeric matrix proteinChoroidal neovascularizationSubretinal injectionVascular endothelial growth factor

Identifiers

PMID26775053
PMCPMC5862038
OpenAlexW2238008278

What OpenQuestion holds

Textmetadata
LicenceTDM
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.