Inhibitory effects of SU5416, a selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, on experimental corneal neovascularization.
Ključne riječi
Sažetak
OBJECTIVE
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).
CONCLUSIONS
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.
