Gao Lifeng, Huang Mingming, Luo Xiaowen, Song Tao, Wang Xuxia, Wang Zhe, Zhang Wei, Chen Jiangyuan, Lei Hao
Department of Medical Imaging, School of Medicine, Jianghan University, Wuhan 430056, China.
Department of Radiology, Affiliated Hospital of Guiyang Medical University, Guiyang 550008, China.
Magn Reson Imaging. 2020 Sep;71:105-114. doi: 10.1016/j.mri.2020.05.003. Epub 2020 May 17.
Diabetic retinopathy (DR) is one of a major complication of type 1 diabetes mellitus (T1DM) and a leading cause of blindness. Evidence of animal study has shown that it is not only a microvasucular lesion of the eye, but also a neurodegeneration disease of the visual system. However, the in vivo imaging evidence of axonal degeneration in the diabetic optic nerve is scarce. Diffusion tensor imaging (DTI) technique has been proved to be an effective tool to track the integrity of the nerve fibers in the central nervous system. In this study, type 1 diabetes was induced by intraperitoneally injecting a single dose of streptozotocin (STZ) into Sprague-Dawley rats. DTI combined with histological assessments was carried out on the optic nerve to clarify the microstructural alterations underlying DTI indices changes at 4 weeks (4 w), 8 weeks (8 w) and 12 weeks (12 w) after STZ induction. The retinal changes were analyzed by pathological evaluations at 4 weeks (4 w) and 12 weeks (12 w) after STZ induction. DTI results showed significantly decreased mean diffusivity (MD) and axial diffusivity (Da) in diabetic optic nerve compared to controls at 12 w. Atrophy in diabetic nerves was monitored by high resolution T-weighted images. Axonal degeneration without myelin loss of the optic nerve was confirmed by histological examination. Moreover, there are positive correlations between decreased diffusivities (MD and Da) in the optic nerve and reduced total axolemmal area. The diabetic rats showed intense glial activity since 4 w and thinning of the thickness in inner plexiform layer and nerve fiber layer at 12 w in the retina. In conclusion, DTI could in vivo monitor the progression of optic nerve degeneration in diabetes and the findings in our study would help supply axonal protection for DR in preclinical practice.
糖尿病视网膜病变（DR）是1型糖尿病（T1DM）的主要并发症之一，也是失明的主要原因。动物研究证据表明，它不仅是眼部的微血管病变，也是视觉系统的神经退行性疾病。然而，糖尿病视神经轴突退变的体内成像证据稀缺。扩散张量成像（DTI）技术已被证明是追踪中枢神经系统神经纤维完整性的有效工具。在本研究中，通过向Sprague-Dawley大鼠腹腔内注射单剂量链脲佐菌素（STZ）诱导1型糖尿病。在STZ诱导后4周（4 w）、8周（8 w）和12周（12 w），对视神经进行DTI检查并结合组织学评估，以阐明DTI指标变化背后的微观结构改变。在STZ诱导后4周（4 w）和12周（12 w），通过病理评估分析视网膜变化。DTI结果显示，与对照组相比，糖尿病视神经在12 w时平均扩散率（MD）和轴向扩散率（Da）显著降低。通过高分辨率T加权图像监测糖尿病神经的萎缩。组织学检查证实视神经存在轴突退变但无髓鞘丢失。此外，视神经中扩散率（MD和Da）降低与轴突总膜面积减少之间存在正相关。糖尿病大鼠自4 w起显示出强烈的胶质细胞活动，视网膜内丛状层和神经纤维层厚度在12 w时变薄。总之，DTI能够在体内监测糖尿病视神经退变的进展，我们的研究结果将有助于在临床前实践中为糖尿病视网膜病变提供轴突保护。
