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首页> 美国卫生研究院文献>other >Transscleral Sustained Vasohibin-1 Delivery by a Novel Device Suppressed Experimentally-Induced Choroidal Neovascularization
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Transscleral Sustained Vasohibin-1 Delivery by a Novel Device Suppressed Experimentally-Induced Choroidal Neovascularization

机译：经巩膜持续Vasohibin-1递送抑制型试验诱导脉络膜血管生成的新颖的器件

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We established a sustained vasohibin-1 (a 42-kDa protein), delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV) using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]). The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE), and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA) scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device), and vasohibin-1 intravitreal direct injection (0.24 μM) groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.
机译：我们通过使用聚乙二醇二甲基丙烯酸酯，三乙二醇二甲基丙烯酸酯和胶原蛋白微粒的混合物进行光聚合的新方法，建立了一种持续的血管抑制素-1（一种42 kDa的蛋白质）递送装置。我们使用跨巩膜方法在大鼠激光诱导的脉络膜新血管形成（CNV）模型中评估了其作用。我们在设备中使用了可变浓度的vasohibin-1，并使用了酶联免疫吸附测定和Western印迹法来测量释放的vasohibin-1（使用10μMvasohibin-1递送设备时为0.31 nM /天[10VDD]）。当使用内皮管形成评估时，释放的vasohibin-1显示出与天然作用相当的抑制活性。我们还使用了颗粒状血管抑制素-1和异硫氰酸荧光素标记的40 kDa右旋糖酐作为对照。当该装置用于药物递送时，在巩膜上观察到了强烈的荧光素染色，而使用小丸在结膜和周围组织中产生了强染色，但在巩膜上​​没有。植入装置后，在巩膜，脉络膜，视网膜色素上皮（RPE）和神经视网膜中发现了Vasohibin-1。与其他视网膜区域相比，在RPE和神经节细胞层的免疫反应性更强。对于10VDD，VDD（1μMvasohibin-1递送装置）和vasohibin-1玻璃体内直接注射（0.24μM），在RPE脉络膜巩膜的扁平支架中观察到的荧光素血管造影（FA）得分明显较低，CNV面积较小。与微丸，非血管抑制素-1递送装置和玻璃体内媒介物注射组相比。脉络膜新生血管可以使用我们的新型装置经巩膜持续蛋白递送来治疗。我们提供使用跨巩膜方法治疗视网膜疾病的更安全的持续蛋白释放。

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