Evidence map›Paper›PMID 20435587›Full record

ArticleInvestigative ophthalmology & visual science2010

Diabetic eNOS-knockout mice develop accelerated retinopathy.

Qiuhong Li, Amrisha Verma, Ping-Yang Han, Takahiko Nakagawa, Richard J Johnson, Maria B Grant, Martha Campbell-Thompson, Yagna P R Jarajapu, Bo Lei, William W Hauswirth

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
–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

60 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Oxidative Stress Implication in Retinal Diseases-A Review.Antioxidants (Basel, Switzerland) · 2022
    Review
  9. Article
  10. Article
  11. Cellular targets in diabetic retinopathy therapy.World journal of diabetes · 2021
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Nitrosative Stress in Retinal Pathologies: Review.Antioxidants (Basel, Switzerland) · 2019
    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

10 authors.

Qiuhong LiDepartment of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida 32610-0284, USA. qli@ufl.edu
Amrisha Verma
Ping-Yang Han
Takahiko Nakagawa
Richard J Johnson
Maria B Grant
Martha Campbell-Thompson
Yagna P R Jarajapu
Bo Lei
William W Hauswirth

Funding

Gene Therapy for Leber Congenital AmaurosisU10EY013729 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2001 to 2005
$11.5M
NITRIC OXIDE IN THE PATHOGENESIS OF DIABETIC RETINOPATHYR01EY012601 · NEI · UNIVERSITY OF FLORIDA · PI Julia V Busik, Maria Bartolomeo Grant · 1998 to 2026
$9.6M
VISION RESEARCH COREP30EY008571 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 1990 to 2010
$5.5M
Targeting the IGF-1 System in Retinal AngiogenesisR01EY007739 · NEI · UNIVERSITY OF FLORIDA · PI ABCOUWER, STEVEN F, GRANT, MARIA BARTOLOMEO · 1995 to 2015
$5.4M
RETINAL GENE DELIVERY BY ADENO-ASSOCIATED VIRUSR01EY011123 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 1995 to 2009
$3.7M
Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Targeting mitochondrial gene expression in the retinaR01EY016073 · NEI · UNIVERSITY OF FLORIDA · PI LEWIN, ALFRED S · 2005 to 2009
$1.8M
NO Dysregulation of the Peripheral Clock in Diabetic ComplicationsR01DK090730 · NIDDK · UNIVERSITY OF FLORIDA · PI GRANT, MARIA BARTOLOMEO · 2010 to 2013
$1.3M
CXCR4/SDF-1 Axis in Proliferation Diabetic RetinopathyR21EY014818 · NEI · UNIVERSITY OF FLORIDA · PI GRANT, MARIA BARTOLOMEO · 2002 to 2003
$725k
NEI NIH HHS EY016073NEI NIH HHS EY08571NEI NIH HHS EY11123NEI NIH HHS EY13729NEI NIH HHS P30 EY008571NEI NIH HHS P30 EY021721NEI NIH HHS R01 EY007739NEI NIH HHS R01 EY011123NEI NIH HHS R01 EY012601NEI NIH HHS R01 EY016073NEI NIH HHS R21 EY014818NEI NIH HHS U10 EY013729NIDDK NIH HHS R01 DK090730
6 · The paper itself

Abstract

purposeDysfunction of endothelial nitric oxide synthase (eNOS) has been implicated in the pathogenesis of diabetic vascular complications. This study was undertaken to determine the role of eNOS in the development of diabetic retinopathy (DR), by investigating the functional consequences of its deficiency in the diabetic state.

methodsDiabetes was induced in eNOS-knockout (eNOS(-/-)) and C57B/6 mice by streptozotocin (STZ) injection. Retinal vasculature was evaluated by albumin extravasation, to quantitatively measure vascular permeability, and by trypsin-digested retinal vascular preparations, to quantify acellular capillaries. Gliosis was evaluated by immunofluorescent techniques. Retinal capillary basement membrane thickness was assessed by transmission electron microscopy. Total retinal nitric oxide level was assessed by measuring nitrate/nitrite using a fluorometric-based assay, iNOS expression was examined by real-time PCR.

resultsDiabetic eNOS(-/-) mice exhibit more severe retinal vascular permeability than age-matched diabetic C57BL/6 mice, detectable as early as 3 weeks after diabetes induction. Diabetic eNOS(-/-) mice also show earlier onset and an increased number of acellular capillaries, sustained gliosis, and increased capillary basement membrane thickness. Total nitric oxide (NO) level was also increased, concomitant with elevated iNOS expression in diabetic eNOS(-/-) retina.

conclusionsDiabetic eNOS(-/-) mice exhibit A significantly wider range of advanced retinal vascular complications than the age-matched diabetic C57BL/6 mice, supporting the notion that eNOS-derived NO plays an essential role in retinal vascular function. This mouse model also faithfully replicates many of the hallmarks of vascular changes associated with human retinopathy, thus providing a unique model to aid in understanding the pathologic mechanisms of and to develop effective therapeutic strategies for diabetic retinopathy.

Indexed as

AlbuminsAnimalsCapillary PermeabilityDiabetes Mellitus, ExperimentalDiabetic RetinopathyFemaleFluorescein AngiographyFluorescent Antibody Technique, IndirectGlial Fibrillary Acidic ProteinGliosisMaleMiceMice, Inbred C57BLMice, KnockoutNitric OxideNitric Oxide Synthase Type IIAlbuminsGlial Fibrillary Acidic ProteinNitric OxideNitric Oxide Synthase Type IINitric Oxide Synthase Type IIINos2 protein, mouseNos3 protein, mouse

Identifiers

PMID20435587
PMCPMC3066622

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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.