Inhibition of choroidal neovascularization by blocking vascular endothelial growth factor receptor tyrosine kinase

Kami, Junko; Muranaka, Kimimasa; Yanagi, Yasuo; Obata, Ryo; Tamaki, Yasuhiro; Shibuya, Masabumi

doi:10.1007/s10384-007-0506-6

Cited by 32 publications

(22 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They concluded that the KDR selective inhibitor might be beneficial for the treatment of intraocular angiogenic diseases. A recent study performed by Kami et al [36] on experimental choroidal neovascularization also showed significance of Flt-1 and KDR/Flk-1 receptor in choroidal neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of SU5416, a Selective Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, on Experimental Corneal Neovascularization

Keskın

Totan²,

Karadağ³

et al. 2011

Ophthalmic Res

View full text Add to dashboard Cite

Purpose: Treatment of neovascularization in ocular diseases with vascular endothelial growth factor (VEGF) inhibition shows promising results. SU5416 is a low-molecular-weight tyrosine kinase inhibitor. It selectively inhibits the membrane-bound tyrosine kinase activity of VEGF-2 receptor (Flk-1/KDR) and blocks the intracellular signaling process. The aim of this study was to evaluate the effect of SU5416 on corneal neovascularization. Methods: Corneas were cauterized with silver nitrate/potassium nitrate sticks in 20 eyes of 20 BALB/C mice. In the study group (n = 10), SU5416 (25 mg/kg) dissolved in dimethyl sulfoxide was given as an intraperitoneal injection in a single daily dose for 7 days. The other group of 10 mice given intraperitoneal dimethyl sulfoxide alone served as a control group. After 7 days, corneal neovascularization was evaluated using photographs captured by fluorescein angiography. Colored photographs were taken by a biomicroscope with a digital camera. Data were expressed as mean neovascular length and mean number of new vessels for each animal. The values were computed and compared between the groups. Results: The mean burn stimulus intensities were not different between the groups. In the study group, the mean length of the vessels and the mean number of vessels were 0.49 ± 0.05 and 11.20 ± 1.69 mm, respectively. In the control group, the mean length of the vessels and the mean number of the vessels were 0.89 ± 0.11 and 17.80 ± 1.03 mm, respectively. There is a statistically significant difference in the mean length and the mean number of new vessels between the study and control groups (p < 0.001). Conclusion: Selective inhibition of VEGFR-2 (Flk-1/KDR) tyrosine kinase with SU5416 was shown to have an inhibitory effect on corneal neovascularization in this animal model. VEGFR-2 (Flk-1/KDR) tyrosine kinase inhibition may represent a different pathway for treatment of the neovascularization process in ocular pathologies. Fluorescein angiography photographs of new vessels on the cornea may provide a better evaluation of neovascularization than colored images in animal models.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of SU5416, a Selective Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, on Experimental Corneal Neovascularization

Keskın

Totan²,

Karadağ³

et al. 2011

Ophthalmic Res

View full text Add to dashboard Cite

show abstract

“…Daily i.p. injections of SU5416, a VEGF receptor 2 (VEGFR-2) tyrosine kinase inhibitor (49,50), after corneal alkali burn injury significantly reduced the growth of CD31 + blood vessels at day 7 postinjury, abolishing the difference between control and NC-Foxc1 +/− mice ( Fig. 6 A and B).…”

Section: Increased Angiogenic Response Attributable To Foxc1 Haploinsmentioning

confidence: 99%

Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth

Seo

Singh

Lacal

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Normal vision requires the precise control of vascular growth to maintain corneal transparency. Here we provide evidence for a unique mechanism by which the Forkhead box transcription factor FoxC1 regulates corneal vascular development. Murine Foxc1 is essential for development of the ocular anterior segment, and in humans, mutations have been identified in Axenfeld-Rieger syndrome, a disorder characterized by anterior segment dysgenesis. We show that FOXC1 mutations also lead to corneal angiogenesis, and that mice homozygous for either a global (Foxc1

show abstract

“…17,18 Inhibition of VEGF-mediated signaling pathways by blocking VEGFR also suppresses the formation of laser-induced CNV. 10,19,20 SU5416, a novel synthetic compound and an inhibitor of VEGFR-1 and VEGFR-2, suppresses laser-induced CNV in a mouse model, with significant effects produced following both intraperitoneal and intravitreal administration. 10,19 Systematic administration of axitinib, which inhibits receptor tyrosine kinases of VEGFR-1, VEGFR-2, and VEGFR-3, reportedly suppressed and regressed laser-induced CNV.…”

Section: Discussionmentioning

confidence: 99%

“…10,19,20 SU5416, a novel synthetic compound and an inhibitor of VEGFR-1 and VEGFR-2, suppresses laser-induced CNV in a mouse model, with significant effects produced following both intraperitoneal and intravitreal administration. 10,19 Systematic administration of axitinib, which inhibits receptor tyrosine kinases of VEGFR-1, VEGFR-2, and VEGFR-3, reportedly suppressed and regressed laser-induced CNV. 20 Systemically administered DC101, a murine monoclonal antibody against VEGFR-2, also suppressed the formation of CNV.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal Tanibirumab, a Fully Human Monoclonal Antibody Against Vascular Endothelial Growth Factor Receptor 2, Partially Suppresses and Regresses Laser-Induced Choroidal Neovascularization in a Rat Model

Kim

et al. 2014

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

show abstract

Inhibition of choroidal neovascularization by blocking vascular endothelial growth factor receptor tyrosine kinase

Abstract: Both Flt-1 and KDR/Flk-1 have a significant role in CNV formation. Suppression of apoptosis may be involved in the process.

Cited by 32 publications

References 33 publications

Inhibitory Effects of SU5416, a Selective Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, on Experimental Corneal Neovascularization

Inhibitory Effects of SU5416, a Selective Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, on Experimental Corneal Neovascularization

Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth

Intravitreal Tanibirumab, a Fully Human Monoclonal Antibody Against Vascular Endothelial Growth Factor Receptor 2, Partially Suppresses and Regresses Laser-Induced Choroidal Neovascularization in a Rat Model

Contact Info

Product

Resources

About