Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/d-phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

中文翻译：

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仿生手性自组装通过激活代谢途径促进视网膜祖细胞的神经元分化


视网膜变性是一类主要的眼部疾病。迄今为止，视网膜祖细胞（RPC）移植是其最有潜力的治疗方法，其中促进RPC神经元分化仍然是一个尚未解决的挑战。为了解决这个问题，采用创新设计的L/d-苯丙氨酸基手性纳米纤维（LPG和DPG），发现纤维的手性可以有效调节RPC的分化。 qPCR、蛋白质印迹和免疫荧光分析表明，右旋螺旋 DPG 纳米纤维显着促进 RPC 神经元分化，而左旋 LPG 纳米纤维则减弱这种效果。这些效应主要归因于手性螺旋纳米纤维和视黄醇结合蛋白4（RBP4，视黄酸（RA）代谢途径中的关键蛋白）之间的立体选择性相互作用。手性依赖性神经元分化的发现为通过优化手性纳米纤维上移植干细胞的分化来治疗神经退行性疾病提供了新策略。