糖尿病视觉通路病变的磁共振波谱和弥散张量成像研究

The ocular complications of diabetes could cause several diseases leading to blindness. Unfortunately, there is poor apprehension on the diagnosis and intervention of diabetic visual pathway lesions at present. It is quite important to explore the strategies for early diagnosis and specific treatments, which would be based on the manifestation of the pathological and biochemical mechanisms by appropriate methodology. It has been confirmed, by the recent studies and our preliminary work that, retinal nerve fiber layer thinning and visual cortex neuron loss occur in the early stage of diabetes. We suppose that diabetes could cause the apoptosis of retinal ganglion cells even in the early stage, accompanied by metabolic disturbance of glutamate and gamma aminobutyric acid in the neuronal microenvironment, and that neuronal injury closely relate to visual impairment. In this study, we apply magnetic resonance spectroscopy and diffusion tensor imaging technologies to detect the visual pathway lesions in diabetes patients, and elucidate the relationship between the neuronal degeneration and visual function impairment. Also we would measure the retinal function impairment, retinal ganglion cells apoptosis, and retinal metabolism imbalance in the diabetic rats. Taken together, we aim to explore the pathological and biochemical mechanisms of neuronal damage in the visual pathway lesions caused by diabetes. This study would bring benefits for early diagnosis and intervention of visual pathway lesions in diabetes patients.

糖尿病眼部并发症是重要的致盲性疾病。目前临床上糖尿病视觉通路病变的诊断和防治不甚理想，寻找合适的研究方法，阐明其病理和生化机制，由此探索出早期诊断和针对性的治疗方法非常重要。新近报道和课题组前期工作证实，糖尿病早期存在视网膜神经纤维层变薄和视皮质神经元丢失。我们设想，糖尿病早期存在视网膜神经节细胞凋亡，伴随神经元微环境中谷氨酸和γ氨基丁酸等物质代谢异常，神经元损伤与视功能损害密切相关。本课题拟运用磁共振波谱和弥散张量成像技术，1.证实糖尿病大鼠早期存在视网膜功能改变和神经节细胞凋亡，同时伴随视网膜代谢物质平衡失调；2.证实糖尿病患者早期存在视觉通路神经元病变，探讨神经元变性损伤与视功能损害之间的关系；3.探索糖尿病引起视觉通路神经元病变的病理和生化机制。本项目的意义在于能使早期发现并治疗糖尿病视觉通路神经元病变成为可能，为糖尿病神经元变性的早期诊断、早期干预及疾病预后提供依据。

糖尿病所致的眼部并发症较多，且均可致盲。目前临床上糖尿病视觉通路病变的诊断和防治不甚理想，寻找合适的研究方法，阐明其病理和生化机制，由此探索出早期诊断和针对性的治疗方法非常重要。项目组成功建立了1型糖尿病大鼠模型，对糖尿病大鼠模型进行了视网膜和视神经的形态检测，包括HE染色、荧光金逆行标记、免疫组织化学和电镜观察。实验结果均显示在1型糖尿病大鼠模型中视网膜和视神经均存在一定程度的神经损伤性形态学改变。通过荧光金标记RGCs的视网膜铺片以及冰冻切片均可发现糖尿病大鼠RGCs的显著丢失。项目组还对1型糖尿病大鼠进行了活体的7T磁共振波谱分析，检测了大鼠视皮层的代谢物质，结果显示在糖尿病大鼠的视皮层中NAA, Glu, GABA, Tau, Cho相比对照组显著降低，而Ins显著升高。综合分析大鼠视网膜以及视神经形态学观察和视皮层代谢物质改变，推论得知糖尿病发病机制中葡萄糖代谢稳态的破坏可能造成了视皮层代谢物质的改变，并且与视网膜以及视神经中神经细胞的丢失和神经组织的退行性改变有关联。项目组纳入了91例非增殖期糖尿病视网膜病变患者以及100例正常对照组，采用OCT检测了黄斑区视网膜厚度，节细胞层厚度，黄斑区容积以及黄斑中心凹下脉络膜厚度。结果发现相比正常对照组，NPDR患者的黄斑区视网膜厚度，节细胞层厚度，黄斑区容积以及黄斑中心凹下脉络膜厚度均显著下降。本项目从动物实验和临床研究两个方面验证了糖尿病早期存在视觉中枢神经系统的改变，同时探讨了磁共振波谱成像在视觉中枢神经系统病变中的潜在应用价值，为糖尿病的防治提供了新的思路。