Retinal degenerations, which lead to irreversible decline in visual function, are still no effective recovery treatments. Currently, retinal progenitor cell (RPC) transplantation therapy is expected to provide a new approach to treat these diseases; however, the limited proliferation capacity and differentiation potential toward specific retinal neurons of RPCs hinder their potential clinical applications. microRNAs have been reported to serve as important regulators in the cell fate determination of stem/progenitor cells. In this study, our data demonstrated that miR-762 inhibited NPDC1 expression to positively regulate RPC proliferation and suppress RPC neuronal differentiation. Furthermore, the knockdown of miR-762 upregulated NPDC1 expression in RPCs, leading to the inhibition of RPC proliferation and the increase in neuronal differentiation. Moreover, NPDC1 could rescue anti-miR-762-induced RPC proliferation deficiency and the inhibitory effect of miR-762 on RPC differentiation. In conclusion, our study demonstrated that miR-762 plays a crucial role in regulating RPC proliferation and differentiation by directly targeting NPDC1, which is firstly reported that microRNAs positively regulate RPC proliferation and negatively regulate RPC differentiation, which provides a comprehensive understanding of the molecular mechanisms that dominate RPC proliferation and differentiation in vitro.

导致视觉功能不可逆下降的视网膜变性仍然没有有效的恢复治疗方法。目前，视网膜祖细胞（RPC）移植疗法有望提供治疗这些疾病的新方法；然而，RPCs 对特定视网膜神经元的有限增殖能力和分化潜力阻碍了其潜在的临床应用。据报道，microRNA 在干细胞/祖细胞的细胞命运决定中充当重要的调节因子。在这项研究中，我们的数据表明 miR-762 抑制 NPDC1 表达以正调节 RPC 增殖并抑制 RPC 神经元分化。此外，敲除 miR-762 上调 RPC 中 NPDC1 的表达，导致 RPC 增殖受到抑制和神经元分化增加。此外，NPDC1 可以挽救抗 miR-762 诱导的 RPC 增殖缺陷和 miR-762 对 RPC 分化的抑制作用。总之，我们的研究表明，miR-762 通过直接靶向 NPDC1 在调节 RPC 增殖和分化中起关键作用，这是首次报道 microRNA 正调节 RPC 增殖和负调节 RPC 分化，这提供了对分子机制的全面理解在体外控制RPC增殖和分化。