Abstract | PURPOSE: METHODS: RESULTS: HGF increased RVP in a time- and dose-dependent manner. HGF-induced RVP was evident 5 minutes after injection, and reached maximal levels after 25 minutes (+107% versus vehicle, P=0.002). This effect was comparable to that of maximum VEGF stimulation (134%+/-128% at 25 ng/mL). Selective inhibitors of MAPK ( PD98059) and PI-3 kinase ( LY294002) suppressed HGF-induced RVP by 86%+/-44% (P=0.015) and 97%+/-59% (P=0.021), respectively. Non- isoform-selective inhibition of PKC did not significantly decrease HGF-induced RVP. Although VEGF increases RBF and reduces MCT, HGF did not affect either. CONCLUSIONS: HGF increases RVP in a time- and dose-dependent manner at physiologically relevant concentrations with a magnitude and profile similar to that of VEGF, without affecting retinal hemodynamics. Thus, HGF may represent another clinically significant contributor to retinal edema distinct from the actions of VEGF.
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Authors | Allen C Clermont, Mark Cahill, Haytham Salti, Susan L Rook, Christian Rask-Madsen, Lucy Goddard, Jun S Wong, Dahlia Bursell, Sven E Bursell, Lloyd Paul Aiello |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 47
Issue 6
Pg. 2701-8
(Jun 2006)
ISSN: 0146-0404 [Print] United States |
PMID | 16723489
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- HGF protein, human
- Phosphoinositide-3 Kinase Inhibitors
- Hepatocyte Growth Factor
- Protein Kinase C
- Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Blood Circulation
- Blotting, Western
- Capillary Permeability
(drug effects)
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(pharmacology)
- Fluorescein Angiography
- Fluorophotometry
- Hemodynamics
(physiology)
- Hepatocyte Growth Factor
(pharmacology)
- Male
- Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphoinositide-3 Kinase Inhibitors
- Protein Kinase C
(antagonists & inhibitors, metabolism)
- Rats
- Rats, Sprague-Dawley
- Regional Blood Flow
- Retinal Vessels
(enzymology, physiology)
- Time Factors
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