Department of Radiology. The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital & Cancer Center, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan, PR China.
Department of Radiology. The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital & Cancer Center, No. 519 Kunzhou Road, Xishan District, Kunming, 650118, Yunnan, PR China.
Neurotoxicology. 2020 Mar;77:145-154. doi: 10.1016/j.neuro.2020.01.008. Epub 2020 Jan 24.
Radiation-induced optic neuropathy (RION) is a serious complication that occurs after radiation therapy of tumors in the vicinity of the optic nerve, yet its mechanism and imaging features are poorly understood. In this study, we employed manganese-enhanced MRI (MEMRI) to assess optic nerve axonal transport in tree shrews and rats after irradiation.
A comparison of normal visual projections in tree shrews and rats was conducted by intravitreal MnCl injection followed by MRI. Adult male tree shrews and rats received a total dose of 20 Gy delivered in two fractions (10 Gy per fraction) within 5 days. Longitudinal MEMRI was conducted 5, 10, 20 and 30 weeks after radiation. At the end of observation, motor proteins involved in axonal transport were detected by western blotting, and the axon cytoskeleton was assessed by immunofluorescence.
The eyeballs, lens sizes, vitreous volumes, optic nerves and superior colliculi of tree shrews were significantly larger than those of rats on MEMRI (P < 0.05). The Mn-enhancement of the optic nerve showed no significant changes at 5 and 10 weeks (P > 0.05) but decreased gradually from 20 to 30 weeks postirradiation (P < 0.05). The enhancement of the superior colliculus gradually decreased from 5 weeks to 30 weeks, and the decrease was most significant at 30 weeks (P < 0.05). The levels of the motor proteins cytoplasmic dynein-1, kinesin-1 and kinesin-2 in the experimental group were significantly decreased (P < 0.05). The immunofluorescence results showed that the α-tubulin, β-tubulin and SMI 31 levels in the experimental groups and control groups were not significantly different (P > 0.05).
Tree shrews show great advantages in visual neuroscience research involving MEMRI. The main cause of the decline in axonal transport in RION is an insufficient level of motor protein rather than damage to the axonal cytoskeletal structure. Longitudinal MEMRI can be used to detect changes in axonal transport function and to observe the relatively intact axon structure from the early to late stages after radiation administration.
放射性视神经病变（RION）是一种严重的并发症，发生在视神经附近的肿瘤放射治疗后，但它的机制和影像学特征尚未被充分了解。在这项研究中，我们使用锰增强 MRI（MEMRI）来评估树鼩和大鼠照射后视神经轴突运输的情况。
通过玻璃体内注射 MnCl2 后进行 MRI 比较，观察树鼩和大鼠的正常视觉投射。成年雄性树鼩和大鼠在 5 天内接受 20Gy 的总剂量，分为 2 个部分（10Gy/部分）。照射后 5、10、20 和 30 周进行纵向 MEMRI。观察结束时，通过 Western blot 检测参与轴突运输的运动蛋白，通过免疫荧光法评估轴突细胞骨架。
在 MEMRI 上，树鼩的眼球、晶状体大小、玻璃体体积、视神经和上丘均明显大于大鼠（P<0.05）。照射后 5 周和 10 周，视神经 Mn 增强无明显变化（P>0.05），但从 20 周逐渐下降至 30 周（P<0.05）。上丘的增强逐渐从 5 周下降到 30 周，30 周时下降最明显（P<0.05）。实验组的细胞质动力蛋白 1、驱动蛋白 1 和驱动蛋白 2 的运动蛋白水平明显降低（P<0.05）。免疫荧光结果显示，实验组和对照组的α-微管蛋白、β-微管蛋白和 SMI 31 水平无明显差异（P>0.05）。
树鼩在涉及 MEMRI 的视觉神经科学研究中具有很大的优势。RION 中轴突运输下降的主要原因是运动蛋白水平不足，而不是轴突细胞骨架结构的损伤。纵向 MEMRI 可用于检测轴突运输功能的变化，并从照射后早期到晚期观察相对完整的轴突结构。
