Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy
Florian Sennlaub, … , Yves Courtois, Olivier Goureau
Florian Sennlaub, … , Yves Courtois, Olivier Goureau
Published March 15, 2001
Citation Information: J Clin Invest. 2001;107(6):717-725. https://doi.org/10.1172/JCI10874.
View: Text | PDF
Article Article has an altmetric score of 3

Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy

  • Text
  • PDF
Abstract

Intravitreal neovascular diseases are a major cause of blindness worldwide. It remains unclear why neovessels in many retinal diseases spread into the physiologically nonvascularized vitreous rather than into the ischemic retinal areas, where the angiogenic factors are released. Here we show that inducible nitric oxide synthase (iNOS) is expressed in the ischemic retina. Using iNOS knockout mice and the iNOS inhibitor 1400W, we demonstrate that iNOS expression inhibits angiogenesis locally in the avascular retina, mediated at least in part by a downregulation of VEGF receptor 2 (VEGFR2) in cells adjacent to iNOS-expressing cells. At the same time, pathological intravitreal neovascularization is considerably stronger in iNOS-expressing animals. These findings demonstrate that iNOS plays a crucial role in retinal neovascular disease and show that it offers an ideal target for the control of vitreal neovascularization through improvement of the vascularization of the hypoxic retina.

Authors

Florian Sennlaub, Yves Courtois, Olivier Goureau

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Quantification of ischemic retina (a–g) and intravitreal neovascularizat...
Quantification of ischemic retina (a–g) and intravitreal neovascularization (h–j). (g) Capillary-free area as a percentage of total retinal surface in FITC-dextran–perfused retinae of oxygen-incubated iNOS+/+ mice (a–c) and iNOS–/– (d–f) mice at different stages. On P12, no difference in the size of the capillary-free area in iNOS+/+ (a) and iNOS–/– (d) mice is detectable. Nor is there any significant difference at P14 after 48 hours of hypoxia (b [iNOS+/+], e [iNOS–/–]). At P17, retinal flat-mounts of oxygen-incubated iNOS–/– mice (f) reveal a significant reduction in the size of the central capillary-free area and a relatively normal vascular morphology compared with retinae of oxygen-incubated iNOS+/+ mice (c). AP < 0.0001; n = 6. Picture side length a–f = 5.150 mm. (j) Intravitreal neovascularization quantified by endothelial cell nucleus count on serial sections. On P14, a weak equivalent neovascular response is detected in iNOS+/+ and iNOS–/– oxygen-exposed mice (n = 5). At P17, the intravitreal neovascularization is significantly stronger in the iNOS+/+ mice (h, arrowheads) compared with iNOS–/– mice (i). BP < 0.0001; n = 10. Counts at P20 reveal a similar difference (CP < 0.0001; n = 5). Picture side width (h, i) = 220 μm.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 1 patents
28 readers on Mendeley
See more details