Bull Natalie D, Irvine Karen-Amanda, Franklin Robin J M, Martin Keith R
Centre for Brain Repair and National Institute for Health Research)Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom.
Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4244-53. doi: 10.1167/iovs.08-3239. Epub 2009 Apr 8.
Glaucoma is a common neurodegenerative disease for which current therapies are often insufficient; thus, new neuroprotective strategies are an important goal. Stem cells are attracting increasing attention as mediators of neuroprotection, often conferred via the trophic support of injured neurons. The purpose of our investigation was to determine whether oligodendrocyte precursor cells (OPCs), a type of neural stem cell, can protect retinal ganglion cells (RGCs) from glaucomatous damage in vivo.
Intraocular pressure was chronically increased by trabecular laser treatment delivered unilaterally to adult rat eyes. OPCs were isolated in vitro and then transplanted intravitreally either before, or concurrent with, injury induction. Survival, migration, differentiation, and integration of grafted cells were assessed by immunohistochemistry. RGC survival was assessed by optic nerve axon quantification.
Transplanted OPCs were found to survive within the eye for at least 12 weeks and to localize close to the RGCs. Moreover, OPCs significantly enhanced the survival of RGCs in the glaucomatous eye, but only when concomitantly activated by inflammation. Axonal loss relative to the untreated fellow eye was 28.34% +/- 11.51% in eyes that received activated OPCs, compared with 60.34% +/- 8.28% in control eyes (mean +/- SEM; P = 0.05). Amelioration of RGC death was not attributable to inflammation but relied on an interaction between inflammatory cells and OPCs. Engrafted cells also displayed multipotentiality in vivo.
The impressive neuroprotection conferred by OPCs in this model suggests stem cell-based therapies should be explored further as a potential treatment for glaucoma.
青光眼是一种常见的神经退行性疾病，目前的治疗方法往往效果不佳；因此，新的神经保护策略是一个重要目标。干细胞作为神经保护的介质正受到越来越多的关注，其神经保护作用通常是通过对受损神经元的营养支持来实现的。我们研究的目的是确定少突胶质前体细胞（OPCs），一种神经干细胞，是否能在体内保护视网膜神经节细胞（RGCs）免受青光眼性损伤。
通过对成年大鼠单侧眼睛进行小梁激光治疗，使眼压长期升高。在体外分离OPCs，然后在损伤诱导前或诱导时经玻璃体注射移植。通过免疫组织化学评估移植细胞的存活、迁移、分化和整合。通过视神经轴突定量评估RGC的存活情况。
发现移植的OPCs在眼内存活至少12周，并定位于靠近RGCs的位置。此外，OPCs显著提高了青光眼眼中RGCs的存活率，但只有在同时被炎症激活时才有效。与未治疗的对侧眼相比，接受激活的OPCs的眼中轴突损失率为28.34%±11.51%，而对照眼中为60.34%±8.28%（平均值±标准误；P = 0.05）。RGC死亡的改善并非归因于炎症，而是依赖于炎症细胞与OPCs之间的相互作用。移植的细胞在体内也表现出多能性。
该模型中OPCs所提供的显著神经保护作用表明，基于干细胞的治疗方法应作为青光眼的一种潜在治疗手段进行进一步探索。
