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人脐带血间充质干细胞(hUCB-MSCs)对急性视神经损伤的抗凋亡和神经保护作用是短暂的。

The anti-apoptotic and neuro-protective effects of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) on acute optic nerve injury is transient.

机构信息

Department of Ophthalmology of Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.

出版信息

Brain Res. 2013 Sep 26;1532:63-75. doi: 10.1016/j.brainres.2013.07.037. Epub 2013 Aug 8.

Abstract

Progressive death of retinal ganglion cells (RGCs) is a major cause of irreversible visual impairment after optic nerve injury. Clinically, there are still no effective treatments for recovering the visual function at present. The probable approaches to maintain the vision and RGCs function involve in preventing RGCs from death and/or promoting the regeneration of damaged RGCs. Previous studies have shown that mesenchymal stem cells (MSCs) take neuroprotective effects on ischemia-induced cortical and spinal cord injury, however, whether MSCs have a beneficial effect on the optical nerve injury is not clearly determined. In present study, we transplanted MSCs derived from human umbilical cord blood (hUCB-MSCs) into the vitreous cavity of adult rats and investigated the probable capacity of anti-apoptosis and pro-neuroprotective effects on RGCs. RGCs were retrogradely traced by fluorescent gold particles (FG); cellular apoptosis was investigated by caspase-3 immunohistochemistry and terminal dUTP nick end labeling (TUNEL) staining. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of the retina. Growth associated protein 43 (GAP-43), an established marker for axonal regeneration, was used to visualize the regenerative process over time. Expression of P2X7 receptors (P2X7R), which are responsible for inflammatory and immune responses, was also monitored in our experiments. We found that the hUCB-MSC transplantation significantly decreased cellular apoptosis and promoted the survival of RGCs in early phase. However, this protection was transient and the RGCs could not be protected from death in the end. Consistent with apoptosis detection, P2X7R was also significantly decreased in hUCB-MSC transplanted rats in the early time but without obvious difference to the rats from control group in the end. Thus, our results imply that hUCB-MSCs take anti-apoptotic, pro-neuroregenerative and anti-inflammatory effects in the early time for acute optic nerve injury in adult rats but could not prevent RGCs from death eventually.

摘要

视网膜神经节细胞(RGCs)的进行性死亡是视神经损伤后不可逆视力损害的主要原因。临床上,目前仍然没有有效的治疗方法来恢复视觉功能。维持视力和 RGC 功能的可能方法包括防止 RGC 死亡和/或促进受损 RGC 的再生。先前的研究表明,间充质干细胞(MSCs)对缺血性皮质和脊髓损伤具有神经保护作用,然而,MSCs 是否对视神经损伤有有益影响尚不清楚。在本研究中,我们将人脐血来源的间充质干细胞(hUCB-MSCs)移植到成年大鼠的玻璃体腔中,研究其对 RGC 可能的抗凋亡和神经营养作用。通过荧光金颗粒(FG)逆行追踪 RGC;通过 caspase-3 免疫组化和末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)染色检测细胞凋亡。苏木精-伊红(HE)染色观察视网膜形态变化。生长相关蛋白 43(GAP-43)是轴突再生的公认标志物,用于随时间可视化再生过程。还监测了 P2X7 受体(P2X7R)的表达,P2X7R 负责炎症和免疫反应。我们发现 hUCB-MSC 移植显著减少了细胞凋亡并促进了早期 RGC 的存活。然而,这种保护是短暂的,最终 RGC 仍无法避免死亡。与凋亡检测一致,在早期 hUCB-MSC 移植大鼠中 P2X7R 也显著降低,但与对照组大鼠最终无明显差异。因此,我们的结果表明,hUCB-MSCs 在成年大鼠急性视神经损伤的早期具有抗凋亡、神经营养和抗炎作用,但最终无法防止 RGC 死亡。

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