Effect of VEGF Trap on Normal Retinal Vascular Development and Oxygen-Induced Retinopathy in the Dog
Effect of VEGF Trap on Normal Retinal Vascular Development and Oxygen-Induced Retinopathy in the Dog
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DOI：
10.1167/iovs.10-6798
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发表时间：
2011-06-01
影响因子：
4.4
通讯作者：
Wiegand, Stanley J.
中科院分区：
文献类型：
--
作者：
Lutty, Gerard A.;McLeod, D. Scott;Wiegand, Stanley J.
目的。目的探讨血管内皮生长因子诱捕器（VEGF trap）对氧致视网膜病变（OIR）犬视网膜血管发育和病理性新生血管（NV）的影响。新生狗（出生后一天[P]1）暴露于100% O(2)，然后在P5返回室内空气。在P8，空气控制和氧气处理犬的一只眼玻璃体内注射VEGF Trap(5、25或250 μ g)，在另一只眼注射人FC （hFc）。P21检查视网膜血管和NV。其他氧暴露动物在确认早产儿视网膜病变（ROP）样病理后，在P22接受5 μ g VEGF Trap或hFc，并在p45进行评估。在空气对照中，250 μ g或25 μ g VEGF陷阱注射的眼睛视网膜血管化面积和浅表毛细血管密度均减少，深部毛细血管缺失。接受5毫克剂量的眼睛与对照组无法区分。在氧处理的动物中，所有注射了VEGF Trap的眼睛的玻璃体内NV明显低于注射了hfc的眼睛，无论剂量如何。注射250 μ g或25 μ g VEGF Trap后，OIR动物的视网膜血管面积明显减少，但5 μ g剂量未抑制视网膜血管重建。在P22时接受5 μ g VEGF诱捕术的已有NV的眼睛在p45时显示出相当大的OIR病理分辨率。VEGF Trap抑制NV的形成，但在P8注射时，高剂量也抑制视网膜血运重建。相反，最低剂量能有效阻断NV并使已有的NV消退，而对血管生成或视网膜血运重建没有明显影响。这些发现表明，在考虑使用vegf靶向药物治疗ROP时，剂量选择是一个重要的变量。（中国眼科杂志，2010;51:4039-4047）DOI:10.1167/iovs.10-6798
PURPOSE. To evaluate the effects of a vascular endothelial growth factor trap (VEGF Trap) on retinal vascular development and pathologic neovascularization (NV) in the canine model of oxygen-induced retinopathy (OIR).METHODS. Newborn dogs (postnatal day [P]1) were exposed to 100% O(2) and then returned to room air on P5. VEGF Trap (5, 25, or 250 mu g) was injected intravitreally in one eye and human FC (hFc) injected in the fellow eye of air control and oxygen-treated dogs on P8. The retinal vasculature and NV were evaluated on P21. Other oxygen-exposed animals received 5 mu g of VEGF Trap or hFc on P22 after confirmation of retinopathy of prematurity (ROP)-like pathology and were evaluated at P45.RESULTS. In air controls, both the vascularized area of the retina and the density of superficial capillaries were reduced in 250 or 25 mu g VEGF Trap-injected eyes, and deep capillaries were absent. Eyes that received the 5 mu g dose were indistinguishable from controls. In oxygen-treated animals, all eyes injected with VEGF Trap exhibited markedly less intravitreal NV than that of hFc-injected fellow eyes, irrespective of dose. Retinal vascular area in OIR animals was significantly reduced in eyes injected with 250 or 25 mu g of VEGF Trap, but the 5 mu g dose did not inhibit retinal revascularization. Eyes with existing NV that received 5 mu g VEGF Trap at P22 exhibited substantial resolution of OIR pathology at P45.CONCLUSIONS. The VEGF Trap inhibited the formation of NV, but higher doses also inhibited revascularization of retina when injected at P8. In contrast, the lowest dose tested effectively blocked NV and caused regression of existing NV, without appreciably affecting vasculogenesis or retinal revascularization. These findings suggest that dose selection is an important variable when considering the use of VEGF-targeting agents for the treatment of ROP. (Invest Ophthalmol Vis Sci. 2010;51: 4039-4047) DOI:10.1167/iovs.10-6798