Elevated mRNA expression of brain-derived neurotrophic factor in retinal ganglion cell layer after optic nerve injury.
Elevated mRNA expression of brain-derived neurotrophic factor in retinal ganglion cell layer after optic nerve injury.
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发表时间：
1997-08
影响因子：
4.4
通讯作者：
Hua Gao;Xiaoxi Qiao;Franz Hefti;Joe G. Hollyfield;B. Knusel
中科院分区：
文献类型：
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作者：
Hua Gao;Xiaoxi Qiao;Franz Hefti;Joe G. Hollyfield;B. Knusel
目的近年来的研究表明，外源性脑源性神经营养因子(BDNF)在体内和体外均能促进视网膜神经节细胞存活。BDNF由神经节细胞层(GCL)中的细胞亚群表达。为探讨内源性脑源性神经营养因子在神经节细胞损伤后的神经元保护中的作用，观察了视神经损伤后视网膜中脑源性神经营养因子的表达。方法将SD大鼠的视神经在视盘后部行眶内挤压。在对照组中，每只动物对侧的视神经都同样暴露在外面，但没有被挤压。在间隔6小时至6周后，对眼组织进行原位杂交、Northern印迹和核糖核酸酶保护检测。结果ON损伤后，仅GCL细胞BDNF表达显著升高，且表达BDNF的细胞数多于对照组。脑源性神经营养因子的表达在伤后24小时开始升高，48小时达高峰，2周后降至基础水平。定量分析显示，损伤后48h，GCL单个细胞的BDNF阳性细胞数增加了5~6倍，信号强度增加了54%。在未损伤的对照视网膜中，BDNF的表达定位于GCL中的一些细胞，与未手术的正常眼相同。Northern印迹和核糖核酸酶保护分析显示，损伤后48h，BDNF的表达较对照水平升高了38%。结论神经节细胞轴索损伤后，GCL细胞可上调BDNF的基因表达，提示内源性BDNF可能参与了神经节细胞轴突损伤后的自然神经保护过程。
PURPOSE Recent studies show that exogenous brain-derived neurotrophic factor (BDNF) can promote retinal ganglion cell survival in vivo and in vitro. BDNF is expressed by a subpopulation of cells in the ganglion cell layer (GCL). To investigate whether endogenous BDNF may play a role in neuronal protection after ganglion cell trauma, BDNF expression in the retina was examined after optic nerve (ON) injury. METHODS The optic nerve in Sprague-Dawley rats was crushed intraorbitally posterior to the optic disc. For controls, the optic nerve on the opposite side in each animal was similarly exposed but was not crushed. After intervals of 6 hours to 6 weeks, eye tissues were processed for in situ hybridization, Northern blot, and RNase protection assay using radiolabeled rat riboprobes. RESULTS After ON injury, BDNF expression was significantly elevated in cells restricted to the GCL, and more cells demonstrated expression of BDNF than were observed in the controls. Elevated BDNF expression was first observed at 24 hours, peaked at 48 hours, and declined to the basal level 2 weeks after ON injury. Quantitative analysis showed a fivefold to sixfold increase in the number of BDNF-positive cells and a 54% increase in BDNF signal intensity in individual cells in the GCL 48 hours after ON injury. In control retinas without ON injury, BDNF expression was localized to some cells in the GCL, as was observed in normal eyes without surgery. Northern blot and RNase protection assay demonstrated a 38% elevation in BDNF expression above control levels 48 hours after ON injury. CONCLUSIONS These results indicate that cells in the GCL can upregulate gene expression of BDNF in response to ganglion cell axonal injury and suggest that endogenous BDNF may contribute to a natural neuroprotective process after ON injury.