Section of Retinal Ganglion Cell Biology, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Invest Ophthalmol Vis Sci. 2018 Nov 1;59(13):5473-5480. doi: 10.1167/iovs.18-25310.
To determine if bone marrow-derived stem cell (BMSC) small extracellular vesicles (sEV) promote retinal ganglion cell (RGC) neuroprotection in the genetic DBA/2J mouse model of glaucoma for 12 months.
BMSC sEV and control fibroblast-derived sEV were intravitreally injected into 3-month-old DBA/2J mice once a month for 9 months. IOP and positive scotopic threshold responses were measured from 3 months: IOP was measured monthly and positive scotopic threshold responses were measured every 3 months. RGC neuroprotection was determined in wholemounts stained with RNA binding protein with multiple splicing (RBPMS), whereas axonal damage was assessed using paraphenylenediamine staining.
As expected, DBA/2J mice developed chronic ocular hypertension beginning at 6 months. The delivery of BMSC sEV, but not fibroblast sEV, provided significant neuroprotective effects for RBPMS+ RGC while significantly reducing the number of degenerating axons seen in the optic nerve. BMSC sEV significantly preserved RGC function in 6-month-old mice, but provided no benefit at 9 and 12 months.
BMSC sEV are an effective neuroprotective treatment in a chronic model of ocular hypertension for 1 year, preserving RGC numbers and protecting against axonal degeneration.
在遗传性 DBA/2J 青光眼小鼠模型中，确定骨髓来源的干细胞（BMSC）小细胞外囊泡（sEV）是否能促进视网膜神经节细胞（RGC）的神经保护作用，时间为 12 个月。
将 BMSC sEV 和对照成纤维细胞衍生的 sEV 每月一次经玻璃体内注射到 3 个月大的 DBA/2J 小鼠中，共注射 9 个月。IOP 和暗适应阈值反应从 3 个月开始测量：IOP 每月测量一次，暗适应阈值反应每 3 个月测量一次。用 RNA 结合蛋白多剪接（RBPMS）对全层片进行染色，以确定 RGC 神经保护作用，而轴突损伤则用对苯二胺染色进行评估。
正如预期的那样，DBA/2J 小鼠从 6 个月开始就出现了慢性眼压升高。BMSC sEV 的递送，但不是成纤维细胞 sEV 的递送，为 RBPMS+RGC 提供了显著的神经保护作用，同时显著减少了视神经中可见的变性轴突数量。BMSC sEV 显著地保留了 6 个月大的小鼠的 RGC 功能，但在 9 个月和 12 个月时没有获益。
BMSC sEV 是一种有效的神经保护治疗方法，可在慢性眼压升高模型中持续 1 年，既能保护 RGC 数量，又能防止轴突退化。
