Department of Neurosurgery, First Affiliated Hospital, Harbin Medical University, Harbin, China.
PLoS One. 2012;7(9):e44360. doi: 10.1371/journal.pone.0044360. Epub 2012 Sep 4.
Research into retinal ganglion cell (RGC) degeneration and neuroprotection after optic nerve injury has received considerable attention and the establishment of simple and effective animal models is of critical importance for future progress.
METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the optic nerves of Wistar rats were semi-transected selectively with a novel optic nerve quantitative amputator. The variation in RGC density was observed with retro-labeled fluorogold at different time points after nerve injury. The densities of surviving RGCs in the experimental eyes at different time points were 1113.69±188.83 RGC/mm² (the survival rate was 63.81% compared with the contralateral eye of the same animal) 1 week post surgery; 748.22±134.75/mm² (46.16% survival rate) 2 weeks post surgery; 505.03±118.67/mm² (30.52% survival rate) 4 weeks post surgery; 436.86±76.36/mm² (24.01% survival rate) 8 weeks post surgery; and 378.20±66.74/mm² (20.30% survival rate) 12 weeks post surgery. Simultaneously, we also measured the axonal distribution of optic nerve fibers; the latency and amplitude of pattern visual evoke potentials (P-VEP); and the variation in pupil diameter response to pupillary light reflex. All of these observations and profiles were consistent with post injury variation characteristics of the optic nerve. These results indicate that we effectively simulated the pathological process of primary and secondary injury after optic nerve injury.
CONCLUSIONS/SIGNIFICANCE: The present quantitative transection optic nerve injury model has increased reproducibility, effectiveness and uniformity. This model is an ideal animal model to provide a foundation for researching new treatments for nerve repair after optic nerve and/or central nerve injury.
视网膜神经节细胞(RGC)变性和视神经损伤后的神经保护研究受到了广泛关注,建立简单有效的动物模型对于未来的进展至关重要。
方法/主要发现:在本研究中,我们使用一种新型的视神经定量切断器选择性地对 Wistar 大鼠的视神经进行半横断。在神经损伤后的不同时间点,用逆行标记的荧光金观察 RGC 密度的变化。实验眼在不同时间点存活的 RGC 密度分别为术后 1 周 1113.69±188.83 个 RGC/mm²(与同一动物对侧眼相比存活率为 63.81%);术后 2 周 748.22±134.75/mm²(存活率为 46.16%);术后 4 周 505.03±118.67/mm²(存活率为 30.52%);术后 8 周 436.86±76.36/mm²(存活率为 24.01%);术后 12 周 378.20±66.74/mm²(存活率为 20.30%)。同时,我们还测量了视神经纤维的轴突分布、图形视觉诱发电位(P-VEP)的潜伏期和振幅以及瞳孔光反射的瞳孔直径变化。所有这些观察和表现都与视神经损伤后的变化特征一致。这些结果表明,我们有效地模拟了视神经损伤后原发性和继发性损伤的病理过程。
结论/意义:本研究建立的定量横断视神经损伤模型具有更高的重现性、有效性和一致性。该模型是研究视神经和/或中枢神经损伤后神经修复新治疗方法的理想动物模型。