中国神经再生研究(英文版) ›› 2021, Vol. 21 ›› Issue (5): 2073-2080.doi: 10.4103/NRR.NRR-D-24-00709

• 原著:视神经损伤修复保护与再生 • 上一篇    

R-28细胞来源细胞外囊泡治疗保护青光眼视网膜的神经节细胞

  

  • 出版日期:2026-05-15 发布日期:2025-08-23

R-28 cell-derived extracellular vesicles protect retinal ganglion cells in glaucoma

Esmahan Durmaz1 , Maryam Esmaeili1 , Philip Lewis1 , Gloria Cimaglia1, 2, Aled Clayton3 , Ben Mead1, *   

  1. 1 School of Optometry and Vision Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK;  2 Dementia Research Institute, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK;  3 School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
  • Online:2026-05-15 Published:2025-08-23
  • Contact: Ben Mead, PhD, MeadB@Cardiff.ac.uk.
  • Supported by:
    ED was supported by a Ph.D. scholarship from the YLSY program of the Republic of Turkiye, Ministry of National Education. BM was also funded by Fight for Sight UK, grant reference # 5183/5184.

摘要:

青光眼的特征是慢性进行性视神经损伤和视网膜神经节细胞死亡。尽管对视网膜神经节细胞的神经保护进行了大量研究,但目前仍没有可用于临床的治疗方法。最近的证据表明,从多种干细胞中分离出的细胞外囊泡对视网膜神经节细胞神经保护具有疗效。实验对视网膜祖细胞R-28细胞系的新型细胞外囊泡来源进行了体外和体内测试。从 R-28 细胞中分离并鉴定了细胞外囊泡,并在体外和体内青光眼模型中测试了它们对视网膜神经节细胞存活的疗效,检测了视网膜神经节细胞的存活率及其轴突的保存情况。裕还检测了细胞外囊泡对从人类胚胎干细胞分化而来的视网膜神经节细胞的神经保护能力,并研究了 R-28细胞外囊泡处理后视网膜神经节细胞中 miRNA 的变化,预测了可能的调节途径。R-28 细胞外囊泡提高了视网膜神经节细胞的存活率,但未能显著保留轴突。研究结果显示了 R-28 细胞外囊泡对人类视网膜神经节细胞的神经保护作用。最后,发现了hsa-miRNA-4443,hsa-miRNA-216a-5p,hsa-let-7e-5p,hsa-miRNA-374b-5p,hsa-miRNA-331-3p和hsa-miRNA-421的表达变化,这可能对视网膜神经节细胞变性具有神经保护潜力。这项研究将为基于miRNA和细胞外囊泡的青光眼神经保护疗法铺平道路。

https://orcid.org/0000-0001-5855-0097 (Ben Mead)

关键词: 细胞外囊泡, 青光眼, miRNA, 神经保护, R-28细胞系, 视网膜神经节细胞

Abstract: Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death. Although extensive research has been conducted on neuroprotection for retinal ganglion cells, there is still no treatment for clinical use. Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection. In this study, we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo. We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model, measuring retinal ganglion cell survival and preservation of their axons. Additionally, we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells. Finally, we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment, and predicted possible pathways that may be modulated. R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly. Moreover, the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells. Finally, we also showed changes in hsa-miRNA-4443, hsa-miRNA-216a-5p, hsa-let-7e-5p, hsa-miRNA-374b-5p, hsa-miRNA-331-3p, and hsa-miRNA-421 expressions, which may have neuroprotective potential on retinal ganglion cell degeneration. This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.

Key words: extracellular vesicles, glaucoma, miRNA, neuroprotection, R-28 cell line, retinal ganglion cells