Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Bucheon 31538, Republic of Korea.
Department of Microbiolo and BK21 FOUR Project, Soonchunhyang University College of Medicine, Cheonan 31538, Republic of Korea.
Int J Mol Sci. 2023 Jul 27;24(15):12068. doi: 10.3390/ijms241512068.
Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.
越来越多的证据表明，外泌体参与了视网膜细胞变性，包括其释放不足；因此，它们已成为视网膜病变的重要指标。特别是外泌体 microRNA（miRNA）在调节眼部和视网膜细胞功能方面发挥着重要作用，包括光感受器的成熟、维持和视觉功能。在这里，我们从人类诱导多能干细胞中生成了视网膜类器官（RO），这些细胞在条件培养基中分化了 60 天，之后从 RO 中提取了外泌体（Exo-RO）。随后，我们将 Exo-RO 溶液眼内注射到皇家外科医生学院（RCS）大鼠的眼睛中。眼内注射 Exo-RO 可减少光感受器细胞凋亡，防止外核层变薄，并维持 RCS 大鼠的视觉功能。RNA 测序和 miRNA 分析显示，外泌体中的 miRNAs 主要参与丝裂原活化蛋白激酶（MAPK）信号通路。此外，在 Exo-RO 处理组中，MAPK 相关基因和蛋白的表达明显下降。这些结果表明，Exo-RO 可能是通过靶向 MAPK 信号通路来延缓视网膜变性的一种潜在新策略。
