N-甲基-N-亚硝脲诱导眼科疾病动物模型的潜能探索及治疗保护策略研究

The present investigation is based on the characteristic of the N-methyl- Nnitrosourea(MNU) to induce apoptosis to eye tissues. We intend to induce three types of ophthalmological experimental animal models via different delivery method: the MNU induced retinal degeneration model, the MNU induced cataract model, and the MNU induced corneal endothelial decompensation model. We evaluate systematically the pathological abnormalities of the abovementioned MNU induced animal models via morphological and functional measurements, aiming at exploratiing the potentials of these MNU induced animal models. These questions that disturb the standardization of the models, such as basic pathological properties, optimum application does, accomplishing time point, as well as the dose-effect manner, will be thoroughly. Subsequently, we will complete the physiological data database of the three MNU induced animal models, and establish the control system. This study would promote the standardization of the three MNU induced animal models. On the premise of establishing the stable, objective reference system, this study intends to further develop treatment strategies for specific MNU induced disease model(including the antioxidant therapy by hydrogen rich saline, human embryonic stem cells differentiation and engineering corneal endothelial tissue transplantation).Furthermore, the present study would evaluate the therapeutic effects with the aid of morphological observation, visual function examination, molecular immune method, providing technical supporting and theoretical strategy for the clinical treatment of the aforementioned three ophthalmological diseases.

N-甲基-N-亚硝脲(MNU)是一类具有致畸、致突变功能的亚硝酞胺类烷化物。本项研究以MNU诱导多种眼组织细胞凋亡的特征为线索，经不同给药途径诱导三类眼科疾病动物模型：角膜内皮失代偿、白内障、视网膜退变模动物模型；以动物模型的病理特征标准化评价为基础，系统解决MNU诱导动物模型在成模时间、量效关系、视觉信号通路重塑、临床特征契合度等关键领域亟待解决的科学问题，充分发掘MNU诱导常见眼病动物模型的潜能，藉此规范MNU诱导眼病模型的病生理数据资料库并建立稳定、客观的参照体系，从而为上述眼科疾病动物模型的标准化推广奠定基础。本项研究拟进一步针对具体MNU诱导疾病模型制订针对性治疗策略（包括新型抗氧化治疗，hESCs源种子细胞移植和组织工程角膜内皮移植治疗），借助形态学、免疫组化和视觉功能鉴定等手段进行疗效评价和作用机制探索，以期为上述三类眼病的治疗工作提供思路借鉴和技术支撑。

N-甲基-N-亚硝脲(MNU)是一类具有致畸、致突变功能的亚硝酞胺类烷化物。本项研究以MNU诱导多种眼组织细胞凋亡的特征为线索，经不同给药途径诱导三类眼科疾病动物模型：角膜内皮失代偿、白内障、视网膜变性模动物模型；继而以动物模型的病理特征标准化评价为基础，系统解决MNU诱导动物模型在成模时间、量效关系、视觉信号通路重塑、临床特征契合等关键领域亟待解决的科学问题，充分发掘MNU诱导常见眼病眼科动物模型的潜能，藉此规范完善三类MNU诱导眼科模型的病生理数据资料库并建立稳定、客观的参照体系，从而为上述眼科疾病动物模型的标准化推广奠定基础。本项研究拟进一步针对具体MNU诱导疾病模型制订针对性治疗策略（包括新型抗氧化治疗，电刺激治疗等），借助形态学、免疫组化和视觉功能鉴定等手段进行系统疗效评价，通过实验室技术和蛋白组学的研究进行作用机制探索，以期为上述眼病的治疗工作提供思路借鉴和技术支撑。