Yin Dan-ping, Liu Lin, Cao Li
Department of Ophthalmology, the General Hospital of Jinan Military Command, Jinan 250031, China.
Email:
Zhonghua Yan Ke Za Zhi. 2013 Nov;49(11):1020-8.
This study is to investigate the effect of the combination of the olfactory ensheathing cells (OEC) transplantation and intravitreous injection of ciliary neurotrophic factor (CNTF) on the retinal ganglia cells' (RGC) apoptosis and axonals' reparation and regeneration.
In this study, the supraorbital margin exposure of the optic nerves was used to establish adult SD rats' optic nerve inhausted injury model as control group. Then the purified OECs were injected into the optic nerve sheaths, and CNTF was injected into the vitreous body simultaneously. The rats were divided into control group, CNTF group, OECs group, and OEC+CNTF combined group. At 4 weeks postoperatively, a cholera toxin B subunit (CTB) anterograde tracing technique and fluorescence (FG) biotinylated dextran amine (BDA) retrograde tracing technique were adopted to evaluate the survival of RGC and the regeneration of optic nerve axons. The number of survival neurons of the same vision field and the density of neurons were evaluated by analysis of variance.
At the one and three quadrant distance between optic disc 2 mm spot, the number of the RGC in the control group was significantly (F = 633.38, P < 0.01) decreased compared with the normal group (46.00 ± 1.42, 34.80 ± 1.34, 25.00 ± 1.61, 15.40 ± 2.30). The survived RGC in OEC group was significantly more than that in CNTF group, while the combined treatment with CNTF and OEC had strongest repair effect. The neuron axon density showed a statistically significant difference in the average optical density value at distance between foramen opticum 2 mm spot (OEC+CNTF: 3.18 ± 0.26, OEC: 2.96 ± 0.28, CNTF: 2.83 ± 0.37, and control: 2.75 ± 0.12, respectively, F = 17.66, P < 0.01) .
Optic nerves damage can be repaired and regenerated by the combined treatment with OEC and CNTF suggesting that CNTF and OEC have synergistic effect on the treatment of optic nerve injury and repair. Transplantation of OECs may genetically modify the secretion of human CNTF and promote optic nerve injury repair.
本研究旨在探讨嗅鞘细胞(OEC)移植联合玻璃体内注射睫状神经营养因子(CNTF)对视网膜神经节细胞(RGC)凋亡及轴突修复和再生的影响。
本研究采用眶上缘暴露视神经的方法建立成年SD大鼠视神经挫伤损伤模型作为对照组。然后将纯化的OECs注入视神经鞘内,同时将CNTF注入玻璃体腔。将大鼠分为对照组、CNTF组、OECs组和OEC+CNTF联合组。术后4周,采用霍乱毒素B亚单位(CTB)顺行示踪技术和荧光(FG)生物素化葡聚糖胺(BDA)逆行示踪技术评估RGC的存活及视神经轴突的再生情况。采用方差分析评估同一视野存活神经元的数量和神经元密度。
在视盘2mm处一、三象限距离,对照组RGC数量与正常组相比显著减少(F = 633.38,P < 0.01)(正常组为46.00±1.42、34.80±1.34、25.00±1.61、15.40±2.30)。OEC组存活的RGC明显多于CNTF组,而CNTF与OEC联合治疗的修复效果最强。在视神经孔2mm处距离的平均光密度值方面,神经元轴突密度显示出统计学显著差异(OEC+CNTF组:3.18±0.26,OEC组:2.96±0.28,CNTF组:2.83±0.37,对照组:2.75±0.12,F = 17.66,P < 0.01)。
OEC和CNTF联合治疗可修复和再生视神经损伤,提示CNTF和OEC在视神经损伤治疗和修复中具有协同作用。OEC移植可能在基因水平上改变人CNTF的分泌并促进视神经损伤修复。