Eye Center, Beijing Tsinghua Changgung Hospital, Beijing, 102218, China.
Institute for Precision Medicine, Tsinghua University, Beijing, 100084, China.
Adv Sci (Weinh). 2024 Mar;11(9):e2302940. doi: 10.1002/advs.202302940. Epub 2023 Dec 19.
Choroidal atrophy is a common fundus pathological change closely related to the development of age-related macular degeneration (AMD), retinitis pigmentosa, and pathological myopia. Studies suggest that choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first cells lost in choroidal atrophy. It is found that endothelial cells derived from human pluripotent stem cells (hPSC-ECs) through the MESP1+ mesodermal progenitor stage express CECs-specific markers and can integrate into choriocapillaris. Single-cell RNA-seq (scRNA-seq) studies show that hPSC-ECs upregulate angiogenesis and immune-modulatory and neural protective genes after interacting with ex vivo ischemic choroid. In a rat model of choroidal ischemia (CI), transplantation of hPSC-ECs into the suprachoroidal space increases choroid thickness and vasculature density. Close-up examination shows that engrafted hPSC-ECs integrate with all layers of rat choroidal vessels and last 90 days. Remarkably, EC transplantation improves the visual function of CI rats. The work demonstrates that hPSC-ECs can be used to repair choroidal ischemia in the animal model, which may lead to a new therapy to alleviate choroidal atrophy implicated in dry AMD, pathological myopia, and other ocular diseases.
脉络膜萎缩是一种常见的眼底病理学变化，与年龄相关性黄斑变性 (AMD)、色素性视网膜炎和病理性近视的发展密切相关。研究表明，形成脉络膜毛细血管的脉络膜内皮细胞 (CEC) 是在脉络膜萎缩中首先丢失的细胞。研究发现，通过 MESP1+中胚层祖细胞阶段从人多能干细胞 (hPSC-ECs) 分化而来的内皮细胞表达 CEC 特异性标志物，并能整合到脉络膜毛细血管中。单细胞 RNA 测序 (scRNA-seq) 研究表明，hPSC-ECs 在与体外缺血性脉络膜相互作用后，上调血管生成和免疫调节及神经保护基因。在脉络膜缺血 (CI) 的大鼠模型中，将 hPSC-ECs 移植到脉络膜上腔可增加脉络膜厚度和血管密度。近距离检查显示，移植的 hPSC-ECs 与大鼠脉络膜血管的所有层整合，并持续 90 天。值得注意的是，EC 移植改善了 CI 大鼠的视觉功能。这项工作表明，hPSC-ECs 可用于修复动物模型中的脉络膜缺血，这可能为缓解干性 AMD、病理性近视和其他眼部疾病中涉及的脉络膜萎缩提供一种新的治疗方法。
