Kim and Kim Eye Clinic, Seoul, Korea.
Invest Ophthalmol Vis Sci. 2012 May 31;53(6):3111-9. doi: 10.1167/iovs.11-8499.
We attempt to determine the effect and mechanism of KR-31831 in rat models of corneal neovascularization and choroidal neovascularization (CNV).
Corneal neovascularization was induced by silver nitrate cauterization. Balanced salt solution (for control), KR-31831 (0.1 mg/mL), and bevacizumab (10 mg/mL) were applied topically with or without subsequent subconjunctival injection (10 μL). The degree of corneal neovascularization was compared among treatments. The effects of intravitreal (0.1 and 0.3 mg/mL) and intraperitoneal (25 mg/kg) of KR-31831, and intravitreal injection of bevacizumab (2.5 mg/mL) were compared in a laser-induced CNV model. FITC-dextran was used to observe the choroid vessels and to evaluate vessel leakage by fluorescence intensity.
In the silver nitrate cauterized rat, topical KR-31831 (P = 0.008) or bevacizumab (P = 0.008) reduced effectively the area of corneal neovascularization compared to control on day 14. This was reduced further by additional subconjunctival injection of KR-31831 (P = 0.024) and bevacizumab (P = 0.016). After KR-31831 application, vascular endothelial growth factor (VEGF) receptor 2 and matrix metalloproteinase (MMP)-2 expression was decreased in the cornea. In the CNV model, intravitreal (0.3 mg/mL) and intraperitoneal KR-31831 inhibited significantly the CNV area (P = 0.008 and P = 0.008, respectively) and fluorescence leakage (P = 0.008 and P = 0.032, respectively). This effect was more significant compared to intravitreal bevacizumab in terms of the CNV area (P = 0.032 and P = 0.008, respectively) and fluorescence leakage (P = 0.016 and P = 0.008, respectively).
The anti-angiogenic effect of KR-31831 was comparable in the cornea and more effective in the choroid compared to that of bevacizumab, and it may exert its effect by VEGF signaling and MMP-2.
我们试图确定 KR-31831 在大鼠角膜新生血管和脉络膜新生血管（CNV）模型中的作用和机制。
硝酸银烧灼诱导角膜新生血管。用平衡盐溶液（对照）、KR-31831（0.1mg/ml）和贝伐单抗（10mg/ml）进行局部给药，或在给药后进行结膜下注射（10μl）。比较不同治疗方法的角膜新生血管程度。比较玻璃体内（0.1 和 0.3mg/ml）和腹腔内（25mg/kg）给予 KR-31831 以及玻璃体内注射贝伐单抗（2.5mg/ml）在激光诱导的 CNV 模型中的作用。用 FITC-葡聚糖观察脉络膜血管，并通过荧光强度评估血管渗漏。
在硝酸银烧灼的大鼠中，与对照组相比，局部 KR-31831（P=0.008）或贝伐单抗（P=0.008）在第 14 天可有效减少角膜新生血管面积。通过额外的结膜下注射 KR-31831（P=0.024）和贝伐单抗（P=0.016）可进一步减少角膜新生血管面积。在角膜中，应用 KR-31831 后血管内皮生长因子（VEGF）受体 2 和基质金属蛋白酶（MMP）-2 的表达减少。在 CNV 模型中，玻璃体内（0.3mg/ml）和腹腔内 KR-31831 显著抑制 CNV 面积（P=0.008 和 P=0.008）和荧光渗漏（P=0.008 和 P=0.032）。与玻璃体内贝伐单抗相比，这种效果在 CNV 面积（P=0.032 和 P=0.008）和荧光渗漏（P=0.016 和 P=0.008）方面更为显著。
与贝伐单抗相比，KR-31831 的抗血管生成作用在角膜中相当，在脉络膜中更有效，其作用机制可能是通过 VEGF 信号和 MMP-2。
