MNU的DNA烷基化作用特异诱发感光细胞的凋亡导致视网膜色素变性，但感光细胞对MNU作用高度敏感的原因尚不清楚。我们前期研究表明雌激素对感光细胞有保护作用并发现感光细胞特异表达NDRG家族的NDRG2基因；NDRG2对感光细胞存活具有重要作用，且NDRG2和雌激素作用相关。我们推测二者可能存在协同作用，这种协同作用可能是抵抗DNA烷基化诱导感光细胞凋亡的关键。本项目拟以MNU诱导的感光细胞特异性凋亡为模型，以DNA烷基化为突破口，对比视网膜神经节细胞，研究NDRG2是否与感光细胞对MNU凋亡诱导高度敏感有关；分析NDRG2与雌激素抗MNU诱导感光细胞凋亡的协同作用及其分子机制，以寻找保护感光细胞的新靶点。本项目不仅为揭示DNA烷基化诱导感光细胞特异性凋亡的机理奠定实验基础，也为视网膜色素变性的治疗提供新思路和理论依据。

MNU, an alkylating agent that interacts with DNA, could specifically induce the apoptosis of photoreceptors and lead to retinitis pigmentosa (RP). However, the reason why photoreceptors are highly sensitive to the MNU has been poorly understood. Our previous study has found that: estrogen could protect photoreceptor cells from apoptosis, and NDRG2, a member of NDRG family, expressed specifically in the retinal photoreceptor cells; NDRG2 was crucial for the survival of photoreceptors and NDRG2 was correlated to the function of estrogen. Accordingly it is supposed that a synergistic effect existed between NDRG2 and estrogen and such an effect could be a key for resisting the DNA alkylation induced apoptosis. In this project, in order to find new targets for protecting photoreceptors, by using a model of MNU induced specific apoptosis of photoreceptor cells and focusing on the DNA alkylation, we intend to investigate whether NDRG2 is relevant with the specific sensitivity of photoreceptors to the MNU induced apoptosis contrast with retinal ganglion cells; interpret the synergistic effect and molecular mechanism of the NDRG2 responding to the estrogen signaling preventing the apoptosis of retinal photoreceptor cells. This project will not only establish experimental foundation for explaining the mechanism of the DNA alkylation induced apoptosis of photoreceptors, but also provide theoretical basis and new strategies for the prevention and cure of RP.