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.

Bietti 晶体营养不良 (BCD) 是一种由CYP4V2基因突变引起的常染色体隐性脉络膜视网膜变性。其特征是胆固醇积累和视网膜中的晶体状沉积。羟丙基-β-环糊精 (HP-β-CyD) 通过减少溶酶体功能障碍并抑制从患者来源的 iPS 细胞建立的诱导多能干细胞 (iPSC)-RPE 细胞的细胞毒性，发挥针对 BCD 的治疗作用。然而，HP-β-CyD 的眼部保留率较低，需要改进。因此，本研究使用粘稠剂开发了含有HP-β-CyD的缓释眼用制剂。我们的结果表明，含有 HP-β-CyD 的黄原胶比其他粘稠剂（如甲基纤维素和海藻酸钠）具有显着更高的缓释能力。此外，含有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，它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 的缓慢释放导致游离细胞内胆固醇持续下降。这些结果表明，黄原胶是 HP-β-CyD 缓释制剂的有用底物，并且含有 HP-β-CyD 的黄原胶具有作为 BCD 治疗滴眼剂的潜力。