Development of intraocular lenses of next generation

为了开发用于长期应用和焦距调节的人工晶状体（IOL），研究了以下三个主题。1）观察到的当前IOL的材料劣化机制：为了更深入地了解长期植入后IOL后经常观察到的表面污染，开发了一种从聚合物表面洗脱吸附蛋白质的方法。然后用SDS-聚丙烯酰胺凝胶电泳和蛋白质印迹法分析吸附在聚合物表面的蛋白质。特别注意蛋白质吸附与补体激活的关系以及吸附的补体片段激活巨噬细胞，并对软性丙烯酸IOL中常见的闪光形成机制进行了研究。首先，用原子力显微镜对植入人工晶状体后形成的反光进行显微分析。进一步的体外模拟研究揭示了闪光的形成主要是由于介质温度变化时透镜材料的旋节分解。2）IOL表面的分子设计：为了开发具有良好防污性能、避免蛋白质吸附和细胞粘附的新型IOL，尝试开发用于产生超疏水表面和仿生膜表面的表面改性方法。本文所用的技术包括引入含氟分子和涂覆含磷酰胆碱的聚合物。3）设计具有调节能力的弹性聚合物透镜：选择聚合物水凝胶作为具有调节能力的透镜的组分。利用离子水凝胶的刺激敏感性，证明了制造新的透镜系统的可能性。为丙烯酸-丙烯酰胺共聚物水凝胶透镜的调节提供了基础数据。

In an attempt to develop intraocular lenses(IOLs)for the long-term application and the accommodation of focal length, the following three subjects were studied.1)Mechanisms of material deterioration observed current IOLs : In order to gain deeper insights into the surface fouling that is often observed after the long-term implantation of posterior IOLs, a method for eluting adsorbed proteins from the polymer surface was developed. Then the proteins adsorbed to the polymer surfaces were analyzed with SDS-polyacrylamide gel electrophoresis and the western blotting. A special attention was paid to the relationship between protein adsorption and complement activation and the activation of macrophage by adsorbed complement fragments.The mechanism of glistening formation that is often observed in the soft acryl IOLs was investigated. Firstly the glistenings formed in the explanted IOLs were microscopically analyzed by atomic force microscopy. The further in vitro simulation study reveled that the formation of glistening is primarily due to the spinodal decomposition of the lens materials upon changes in medium temperature.2)Molecular design of IOL surfaces : To develop new IOLs that have good anti-fouling properties, avoiding protein adsorption and cell adhesion, attempts were made to develop surface modification methods for creating super-hydrophobic surfaces and biomembrane-mimetic surfaces. The techniques used here include the introduction of fluorine-containg molecules and the coating of a phosphorylcoline-containing polymer.3)Designing elastic polymer lenses capable of accommodation : Polymeric hydrogels were selected as a component of lenses with accommodative ability. The possibility of fabricating new lens systems was demonstrated, taking an advantage of the stimuli-sensitivity of ionic hydrogels. The basic data were obtained for the accommodation of lenses made of acryamide-acrylic acid copolymer hydrogels.