妊娠糖尿病引起胚胎眼睛发育畸形的机理尚不清楚。近来研究发现高糖环境下眼发育关键因子Pax6的活性受O-GlcNAc糖基化调控，提示妊娠糖尿病致胚胎眼发育畸形的机理可能与Pax6的O-GlcNAc糖基化有关，但尚需科学验证。我们前期研究发现Carnosine类活性肽 (CRP) 能抑制Pax6的O-GlcNAc糖基化，且能修复高糖对鸡胚眼发育的损伤。基于上述结果，本项目拟筛选高特异性CRP小分子探针研究Pax6的O-GlcNAc糖基化在妊娠糖尿病致胚胎眼畸形的作用：在妊娠糖尿病小鼠和高糖鸡胚模型上研究CRP对Pax6 的O-GlcNAc 糖基化生物学功能的影响；研究CRP抑制Pax6的 O-GlcNAc糖基化作用途径；研究CRP经由Pax6 的O-GlcNAc 糖基化转导通路的调控机制。旨在阐明妊娠糖尿病致胚胎眼畸形的发生机理，揭示CRP干预机制，为妊娠糖尿病致胚胎眼畸形的防治提供科学依据。

The exact pathophysiology of embryonic eye malformation caused by gestational diabetes mellitus (GDM) remains poorly understood. Recent studies showed that the activtiy of Pax6, one of the key factors in the process of eye development, can be regulated by O-GlcNAcylation under high concentration of glucose environment. This evidence indicates the key role of O-GlcNAcylation of Pax6 in the pathophysiology of eye malformation, which needs to be proved by scientific study. In our preliminary research, carnosine related peptides (CRP) could inhibit the O-GlcNAcylation of Pax6, and restore the damage of chicken embryo eyes caused by high concentration of glucose. Based on the above results, we plan to choose the molecular probes with high specificity from CRP, by which to study the O-GlcNAcylation of Pax6 in pathophysiology of embryonic eye malformation caused by GDM. For such a purpose, we will determine the effects of CRP on the expression of Pax6, and investigate how CRP inhibits the O-GlcNAcylation of Pax6 by employing GDM mice model and chicken embryo model. The pathway mediated by O-GlcNAcylation of Pax6 in the pathophysiology of eye malformation will be also studied using CRP as small molecular probe. This project aims to clarify the pathophysiology of eye malformation caused by GDM, reveal the protective effects of CRP, and provide scientific evidences for the prevention and treatment of eye malformation caused by GDM.