目前对糖尿病视网膜病变(DR）预防和早期干预主要通过血糖控制。我们近期研究发现糖尿病居民中存在血糖控制稳定后DR仍发生发展的"代谢记忆"现象,其危险因素不明，但已影响到干预效果。代谢记忆分子发病机制关键点是线粒体活性氧（ROS）失衡，前期我们研究已证实UCP-2基因的表达直接调控ROS平衡，而UCP-2、UCP-1或MnSOD2基因位点多态性与DR患病相关，故推测DR代谢记忆发病的个体差异也源于基因多态性，但至今尚无相关研究。鉴于国家自然科学基金现支持眼科流行病学队列研究，本研究拟对已建档的3267名血糖控制稳定的2型糖尿病居民进行连续4年前瞻性队列研究，得到个体特征、生化等预测指标，从而实现DR代谢记忆高危人群早期发现。同时，通过前期病例对照研究和后续队列研究确认与DR代谢记忆相关的UCP-2、UCP-1或MnSOD2基因型，为实现以特定基因型为靶点的DR代谢记忆早期阻断提供理论依据。

The well-accepted strategy for prevention and early-stage treatment of diabetic retinopathy (DR) is maintaining blood glucose in a proper low level. In our previous population-based study, we observed the existence of metabolic memory phenomenon, which describes DR progression in diabetic patients with proper low blood glucose level. Because the related factors of DR metabolic memory incidence in type 2 diabetic patients are still unknown, it is quite difficult to find out high risk patients, and that obviously limits the effects of DR prevention and early-stage treatment strategy. Increasing experimental evidence has shown that unbalanced mitochondrial reactive oxygen species (ROS) activates DR metabolic memory. In our previous and other scientists' studies, uncoupling protein 2 (UCP-2) gene expression are found to regulate retinal mitochondrial ROS balance; UCP-2, UCP-1 and manganese superoxide dismutase 2 (MnSOD2) gene loci polymorphisms are found relevant to DR development. Therefore, we suppose that gene polymorphisms are also correlate with DR metabolic memory phenomenon. However, up til now, there was neither epidemiology report on DR metabolic memory in Chinese population nor association study of specific gene polymorphisms and DR metabolic memory. In the present study, we plan to conduct a 4-year perspective cohort observation of 3267 Chinese type 2 diabetic residents under proper blood glucose control, trying to find out related physical and biochemical risk factors. The results will facilitate discriminating DR high risk groups in diabetic patients who maintain low blood glucose level. In the same time, a prior case-control study and a following cohort study will demonstrate the specific UCP-2, UCP-1 or MnSOD2 gene polymorphism relevant to DR metabolic memory, and that will provide important theoretic evidence of diabetic metabolic memory blocking agents which target on gene polymorphism. The present grant application is in line with the guideline of National Science Foundation of China (NSFC) which now supports cohort epidemiology study on eye diseases.