Wang Ningli, Zeng Mingbing, Ruan Yiwen, Wu Heping, Chen Jingchang, Fan Zhigang, Zhen Huling
Zhongshan Ophthalmic Center, Zhongshan University, Guangzhou 510060, China.
Chin Med J (Engl). 2002 Sep;115(9):1394-400.
To investigate in vivo survival of retinal ganglion cells (RGCs) after partial blockage of optic nerve (ON) axoplasmic flow by sub-retinal space or vitreous cavity injection of brain-derived neural factor (BDNF) produced by genetically modified neural progenitor cells (NPCs).
Adult Sprague-Dawley (SD) rat RGCs were labeled with granular blue (GB) applied to their main targets in the brain. Seven days later, the left ON was intra-obitally crushed with a 40 g power forceps to partially block ON axoplasmic flow. Animals were randomized to three groups. The left eye of each rat received a sham injection, NPCs injection or an injection of genetically modified neural progenitors producing BDNF (BDNF-NPCs). Seven, 15 and 30 days after ON crush, retinas were examined under a fluorescence microscope. By calculating and comparing the average RGCs densities and RGC apoptosis density, RGC survival was estimated and the neuro-protective effect of transplanted cells was evaluated.
Seven, 15 and 30 days after crush, in the intra-vitreous injection group, mean RGC densities had decreased to 1885 +/- 68, 1562 +/- 20, 1380 +/- 7 and 1837 +/- 46, 1561 +/- 58, 1370 +/- 16, respectively with sham injection or neural progenitors injection. However, RGCs density in the groups treated with intra-vitreous injection of BDNF-NPC was 2101 +/- 15, 1809 +/- 19 and 1625 +/- 34. Similar results were found in groups after sub-retinal injection. Higher densities were observed in groups treated with BDNF-NPCs. There were statistically significant differences among groups through nonparametric tests followed by the Mann-Whitely test. RGC apoptosis density in BDNF-NPC at each follow-up time was less than in other groups.
A continuous supply of neurotrophic factors by the injection of genetically modified neural progenitors presents a highly effective approach to counteract optic neuropathy and RGC degeneration after partial ON axoplasmic flow blockage.
通过视网膜下间隙或玻璃体腔注射由基因修饰的神经祖细胞（NPCs）产生的脑源性神经营养因子（BDNF），研究视神经（ON）轴浆流部分阻断后视网膜神经节细胞（RGCs）在体内的存活情况。
成年Sprague-Dawley（SD）大鼠的RGCs用颗粒蓝（GB）标记于其在脑内的主要靶点。7天后，用40g力量的镊子眶内挤压左侧视神经以部分阻断视神经轴浆流。将动物随机分为三组。每组大鼠的左眼接受假注射、NPCs注射或注射产生BDNF的基因修饰神经祖细胞（BDNF-NPCs）。视神经挤压后7天、15天和30天，在荧光显微镜下检查视网膜。通过计算和比较平均RGCs密度和RGC凋亡密度，评估RGCs的存活情况并评价移植细胞的神经保护作用。
挤压后7天、15天和30天，在玻璃体腔注射组中，与假注射或神经祖细胞注射相比，平均RGCs密度分别降至1885±68、1562±20、1380±7和1837±46、1561±58、1370±16。然而，玻璃体腔注射BDNF-NPC治疗组的RGCs密度为2101±15、1809±19和1625±34。视网膜下注射组也发现了类似结果。BDNF-NPCs治疗组观察到更高的密度。通过非参数检验及Mann-Whitely检验，各组间存在统计学显著差异。每个随访时间BDNF-NPC组的RGC凋亡密度均低于其他组。
通过注射基因修饰的神经祖细胞持续供应神经营养因子是一种有效对抗部分视神经轴浆流阻断后视神经病变和RGCs变性的方法。
