Abstract：
Bietti\'s crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-β-CyD is low and needs to be improved. Therefore, this study used a viscous agent to develop a sustained-release ophthalmic formulation containing HP-β-CyD. Our results suggest that HP-β-CyD-containing xanthan gum has a considerably higher sustained release capacity than other viscous agents, such as methylcellulose and sodium alginate. In addition, the HP-β-CyD-containing xanthan gum exhibited pseudoplastic behavior. It was less cytotoxic to human retinal pigment epithelial cells compared with HP-β-CyD alone. Furthermore, the slow release of HP-β-CyD from xanthan gum caused a sustained decrease in free intracellular cholesterol. These results suggest that xanthan gum is a useful substrate for the sustained release formulation of HP-β-CyD, and that HP-β-CyD-containing xanthan gum has potential as an eye drop for BCD treatment.
摘要：
Bietti's晶体营养不良(BCD)是由CYP4V2基因突变引起的常染色体隐性脉络膜视网膜变性。它的特征是胆固醇积累和视网膜中的晶体样沉积物。羟丙基-β-环糊精（HP-β-CyD）通过减少溶酶体功能障碍和抑制从患者来源的iPS细胞建立的诱导多能干细胞（iPSC）-RPE细胞中的细胞毒性来发挥针对BCD的治疗作用。然而,HP-β-CyD的眼保留率低，有待改善。因此,这项研究使用粘性剂开发了含有HP-β-CyD的缓释眼用制剂。我们的结果表明，含HP-β-CyD的黄原胶具有比其他粘性剂高得多的缓释能力，如甲基纤维素和海藻酸钠。此外,含HP-β-CyD的黄原胶表现出假塑性行为。与单独使用HP-β-CyD相比，对人视网膜色素上皮细胞的细胞毒性较小。此外，黄原胶中HP-β-CyD的缓慢释放导致细胞内游离胆固醇的持续降低。这些结果表明，黄原胶是HP-β-CyD缓释制剂的有用底物，含HP-β-CyD的黄原胶具有作为BCD治疗滴眼剂的潜力。
