RGD Reference Report - Suppression of experimental choroidal neovascularization utilizing KDR selective receptor tyrosine kinase inhibitor. - Rat Genome Database

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Suppression of experimental choroidal neovascularization utilizing KDR selective receptor tyrosine kinase inhibitor.

Authors: Takeda, A  Hata, Y  Shiose, S  Sassa, Y  Honda, M  Fujisawa, K  Sakamoto, T  Ishibashi, T 
Citation: Takeda A, etal., Graefes Arch Clin Exp Ophthalmol. 2003 Sep;241(9):765-72. Epub 2003 Aug 23.
RGD ID: 8549716
Pubmed: PMID:12937991   (View Abstract at PubMed)
DOI: DOI:10.1007/s00417-003-0688-7   (Journal Full-text)

BACKGROUND: We investigated the role of the VEGF-VEGF receptor 2 (KDR) system in the development of choroidal neovascularization (CNV) and its possibility as a therapeutic target utilizing KDR selective receptor tyrosine kinase (RTK) inhibitor (SU5416) both in vitro and in an experimental CNV model. METHODS: VEGF-induced phosphorylation of KDR and p44/p42 MAPK in cultured bovine choroidal endothelial cells (BCECs) was determined by Western blot analysis. The proliferation and in vitro tube formation were analyzed by [3H]thymidine uptake and three-dimensional collagen gel model. For experimental CNV model, intense fundus laser photocoagulation was performed on pigmented rats. The anti-angiogenic efficacy of intraperitoneally injected SU5416 on experimental CNV was evaluated by fluorescein angiography and histology. The extent of fluorescein leakage on late-phase angiograms was scored, and the thickness of CNV membrane was histologically measured under a light microscope. RESULTS: VEGF-induced KDR phosphorylation in cultured BCECs was inhibited by SU5416 in a dose-dependent manner (0-3 microM) with IC50 of 0.29 +/- 0.071 microM. SU5416 treatment also resulted in a dose-dependent prohibition of VEGF-induced p44/p42 MAPK phosphorylation, [3H]thymidine uptake and in vitro tube formation with corresponding concentrations that inhibited KDR phosphorylation. The leakage score on fluorescein angiography for experimental CNV was significantly lower in the SU5416-treated group than in the control group (P<0.01). Histologically, the CNV membranes in the SU5416-treated group were 31.6% thinner than those in the control group (P<0.01). CONCLUSION: These results strengthen the evidence for a critical role of the VEGF-KDR system in the development of CNV, indicating that KDR selective inhibitor might be beneficial for the treatment of intraocular angiogenic diseases, including age-related macular degeneration.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Choroidal Neovascularization treatmentISOKdr (Rattus norvegicus)8549716; 8549716 RGD 
Choroidal Neovascularization treatmentIMP 8549716 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdr  (kinase insert domain receptor)

Genes (Mus musculus)
Kdr  (kinase insert domain protein receptor)

Genes (Homo sapiens)
KDR  (kinase insert domain receptor)


Additional Information