Nagai Nobuhiro, Kaji Hirokazu, Nishizawa Matsuhiko, Nakazawa Toru, Abe Toshiaki
Division of Clinical Cell Therapy, Center for Advanced Medical Research and Development (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, 980-8575, Sendai, Japan.
Department of Bioengineering and Robotics, Tohoku University Graduate School of Engineering, 6-6-01 Aramaki-Aoba, Aoba-ku, 980-8579, Sendai, Japan.
Adv Exp Med Biol. 2016;854:471-7. doi: 10.1007/978-3-319-17121-0_63.
We evaluated the effects of a transscleral drug delivery device, consisting of a reservoir and controlled-release cover, which were made of photopolymerized polyethylene glycol dimethacrylate and triethylene glycol dimethacrylate, combined at different ratios. Geranylgeranylacetone (GGA), a heat-shock protein (HSP) inducer, was loaded into the device. The GGA was released from the device under zero-order kinetics. At both 1 week and 4 weeks after device implantation on rat sclera, HSP70 gene and protein expression were up-regulated in the sclera-choroid-retinal pigment epithelium fraction of rat eyes treated with the GGA-loaded device compared with rat eyes treated with saline-loaded devices or eyes of non-treated rats. Flash electroretinograms were recorded 4 days after white light exposure (8000 lx for 18 h). Electroretinographic amplitudes of the a- and b-waves were preserved significantly in rats treated with GGA-loaded devices compared with rats treated with saline-loaded devices. Histological examination showed that the outer nuclear layer thickness was preserved in rats that had the GGA-loaded device. These results may show that transscleral GGA delivery using our device may offer an alternative method to treat retinal diseases.
我们评估了一种经巩膜给药装置的效果,该装置由储液器和控释盖组成,二者由光聚合的聚乙二醇二甲基丙烯酸酯和三乙二醇二甲基丙烯酸酯按不同比例混合制成。将热休克蛋白(HSP)诱导剂香叶基香叶基丙酮(GGA)载入该装置。GGA从装置中以零级动力学方式释放。在将装置植入大鼠巩膜后1周和4周时,与载入生理盐水的装置处理的大鼠眼或未处理大鼠的眼相比,用载入GGA的装置处理的大鼠眼的巩膜-脉络膜-视网膜色素上皮部分中,HSP70基因和蛋白表达上调。在白光暴露(8000勒克斯,持续18小时)4天后记录闪光视网膜电图。与载入生理盐水的装置处理的大鼠相比,用载入GGA的装置处理的大鼠的视网膜电图a波和b波振幅得到显著保留。组织学检查显示,植入载入GGA装置的大鼠的外核层厚度得以保留。这些结果可能表明,使用我们的装置经巩膜递送GGA可能为治疗视网膜疾病提供一种替代方法。