Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Laboratory of Molecular Biology and Histochemistry Joint Research Support Promotion Facility Center for Research Promotion and Support Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
Int J Mol Sci. 2017 Sep 14;18(9):1971. doi: 10.3390/ijms18091971.
We previously prepared ophthalmic formulations containing cilostazol (CLZ) nanoparticles by bead mill methods (CLZ), and found that instillation of CLZ into rat eyes supplies CLZ into the retina. In this study, we investigated changes in the electroretinograms (ERG) of streptozotocin-induced diabetic rats (STZ rats), a model of diabetes mellitus. In addition, we demonstrated that dispersions containing CLZ nanoparticles attenuate changes in the ERG of STZ rats. The instillation of CLZ had no effect on body weight or plasma glucose and insulin levels. Furthermore, no corneal toxicity was observed in the in vivo study using STZ rats. The a-wave and b-wave levels in addition to oscillatory potentials (OP) amplitude decreased in STZ rats two weeks after the injection of streptozotocin, with the instillation of CLZ attenuating these decreases. In addition, the level of vascular endothelial growth factor (VEGF) in the retinas of STZ rats was 9.26-fold higher than in in normal rats, with this increase also prevented by the instillation of CLZ Thus, we have found that a-wave and b-wave levels in addition to OP amplitude are decreased in rats following the injection of excessive streptozotocin. Furthermore, the retinal disorders associated with diabetes mellitus are attenuated by the instillation of CLZ. These findings provide significant information that can be used to design further studies aimed at developing anti-diabetic retinopathy drugs.
我们先前通过珠磨法（CLZ）制备了含有西洛他唑（CLZ）纳米颗粒的眼科制剂，并发现将 CLZ 滴入大鼠眼睛可将 CLZ 输送到视网膜中。在这项研究中，我们研究了链脲佐菌素（STZ）诱导的糖尿病大鼠（STZ 大鼠）模型中视网膜电图（ERG）的变化。此外，我们证明了含有 CLZ 纳米颗粒的分散体可减轻 STZ 大鼠 ERG 的变化。CLZ 的滴注对体重或血浆葡萄糖和胰岛素水平没有影响。此外，在使用 STZ 大鼠的体内研究中未观察到角膜毒性。STZ 大鼠在注射链脲佐菌素两周后，a 波和 b 波水平以及振荡电位（OP）幅度降低，而 CLZ 的滴注可减轻这些降低。此外，STZ 大鼠视网膜中的血管内皮生长因子（VEGF）水平比正常大鼠高 9.26 倍，CLZ 的滴注也可防止这种增加。因此，我们发现，过量注射链脲佐菌素后，大鼠的 a 波和 b 波水平以及 OP 幅度降低。此外，CLZ 的滴注可减轻与糖尿病相关的视网膜病变。这些发现提供了重要的信息，可以用于设计旨在开发抗糖尿病性视网膜病变药物的进一步研究。
