Abstract | PURPOSE:
Nitric oxide (NO) is involved in leukostasis and blood-retinal barrier (BRB) breakdown in the early stages of diabetic retinopathy (DR), but it is unclear which NO synthase (NOS) isoforms are primarily involved. In this study, the authors aimed to clarify the involvement of constitutive (eNOS, nNOS) and inducible NOS (iNOS) isoforms and the mechanisms underlying NO-mediated leukostasis and BRB breakdown. METHODS: RESULTS: Diabetes increased leukostasis within retinal vessels and BRB permeability, which were reduced by L-NAME. Similar effects were observed in diabetic iNOS knockout mice. In diabetic mouse retinas, ICAM-1 protein levels increased, whereas the immunoreactivity of tight junction proteins, occludin and ZO-1 decreased, in correlation with increased protein levels of all NOS isoforms. Those effects were prevented by L-NAME and also in diabetic iNOS knockout mice. High glucose and nitrosative/oxidative stress also increased leukostasis caused by ICAM-1 upregulation. CONCLUSIONS:
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Authors | Ermelindo C Leal, Ayyakkannu Manivannan, Ken-Ichi Hosoya, Tetsuya Terasaki, José Cunha-Vaz, António Francisco Ambrósio, John V Forrester |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 48
Issue 11
Pg. 5257-65
(Nov 2007)
ISSN: 0146-0404 [Print] United States |
PMID | 17962481
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Isoenzymes
- Membrane Proteins
- Occludin
- Ocln protein, mouse
- Ocln protein, rat
- Phosphoproteins
- Tjp1 protein, mouse
- Tjp1 protein, rat
- Zonula Occludens-1 Protein
- Intercellular Adhesion Molecule-1
- Nitric Oxide
- Nitric Oxide Synthase Type II
- NG-Nitroarginine Methyl Ester
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Topics |
- Animals
- Blood-Retinal Barrier
- Blotting, Western
- Capillary Permeability
(physiology)
- Cell Adhesion
- Diabetes Mellitus, Experimental
(enzymology)
- Diabetic Retinopathy
(enzymology)
- Endothelium, Vascular
- Enzyme Inhibitors
(pharmacology)
- Flow Cytometry
- Intercellular Adhesion Molecule-1
(metabolism)
- Isoenzymes
(physiology)
- Leukocytes
(metabolism)
- Leukostasis
(enzymology)
- Male
- Membrane Proteins
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Microscopy, Confocal
- NG-Nitroarginine Methyl Ester
(pharmacology)
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type II
(physiology)
- Occludin
- Ophthalmoscopy
- Phosphoproteins
(metabolism)
- Rats
- Retinal Vessels
(physiology)
- Zonula Occludens-1 Protein
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