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在翼腭动脉结扎诱导的小鼠视网膜缺血再灌注损伤中进行谱系阴性干细胞移植。

Transplantation of lineage-negative stem cells in pterygopalatine artery ligation induced retinal ischemia-reperfusion injury in mice.

作者信息

Minhas Gillipsie, Prabhakar Sudesh, Morishita Ryuichi, Shimamura Munehisa, Bansal Reema, Anand Akshay

机构信息

Neuroscience Research Lab, Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka, Japan.

出版信息

Mol Cell Biochem. 2017 May;429(1-2):123-136. doi: 10.1007/s11010-017-2941-0. Epub 2017 Feb 16.

Abstract

Retinal ischemia is a condition associated with retinal degenerative diseases such as glaucoma, diabetic retinopathy, and other optic neuropathies, leading to visual impairment and blindness worldwide. Currently, there is no therapy available for ischemic retinopathies. Therefore, the aim of this study was to test a murine model of pterygopalatine artery ligation-induced retinal injury for transplantation of mouse bone marrow-derived lineage-negative (lin-ve) stem cells. The mouse external carotid artery and pterygopalatine artery were ligated for 3.5 h followed by reperfusion. The model was validated through fundus fluorescein angiography, laser Doppler and FITC dextran perfusion in whole-mounts. Lin-ve stem cells isolated from mouse bone marrow were transplanted through tail-vein, which showed migration to retina leading to decrease in GFAP expression. The neurotrophic factors such as BDNF and FGF2 showed enhanced expression in the retina. The functional analysis with electroretinogram did not demonstrate any significant changes before or after injury or stem cell transplantation. This study shows a neuroprotective potential in lin-ve stem cells in the retinal ischemia induced by pterygopalatine artery ligation and presents a practical model for validating therapies for ischemic disorders of the retina in future.

摘要

视网膜缺血是一种与青光眼、糖尿病视网膜病变及其他视神经病变等视网膜退行性疾病相关的病症,在全球范围内导致视力损害和失明。目前,尚无针对缺血性视网膜病变的治疗方法。因此,本研究的目的是测试翼腭动脉结扎诱导的视网膜损伤小鼠模型,用于小鼠骨髓来源的谱系阴性(lin-ve)干细胞移植。结扎小鼠颈外动脉和翼腭动脉3.5小时,随后进行再灌注。通过眼底荧光血管造影、激光多普勒和全层FITC葡聚糖灌注对该模型进行验证。从小鼠骨髓中分离出的lin-ve干细胞通过尾静脉移植,显示其迁移至视网膜,导致GFAP表达降低。脑源性神经营养因子(BDNF)和碱性成纤维细胞生长因子2(FGF2)等神经营养因子在视网膜中的表达增强。视网膜电图功能分析未显示损伤或干细胞移植前后有任何显著变化。本研究表明lin-ve干细胞在翼腭动脉结扎诱导的视网膜缺血中具有神经保护潜力,并为未来验证视网膜缺血性疾病的治疗方法提供了一个实用模型。

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