线粒体DNA修复酶0GG1对rds小鼠光感受器细胞氧化损伤的保护作用研究

视网膜色素变性 （RP）是以感光细胞进行性退变为特征的常见不可逆性致盲性眼病，全球患病者累及超过百万，但其损伤机制并不完全清楚，氧化应激被认为是感光细胞凋亡的重要因素，然而目前仍然缺乏有效的保护措施。最新的研究结果证实：线粒体DNA（mtDNA）氧化损伤是疾病早期的始动因素，mtDNA最易受ROS的攻击，同时缺乏类似于核DNA的有效修复，容易形成“mtDNA 损伤-ROS 产生-mtDNA 损伤”恶性循环。本研究拟用线粒体靶向DNA修复酶（MTS-hOGG1），一方面通过体外t-BHP诱导的661W感光细胞氧化损伤模型；另一方面则采用视网色素变性rds小鼠模型， 探讨其对感光细胞mtDNA氧化损伤、ROS产量、线粒体和细胞功能的影响及可能机制。由此阐明mtDNA氧化损伤在上述恶性循环和疾病发展中的源头性致病作用，为确立MTS-hOGG1作为视网膜退行性疾病治疗的新靶点提供更充分的科学依据。

Retinitis pigmentosa is the term given to a set of hereditary retinal diseases that feature degeneration of rod and cone photoreceptors. The worldwide prevalence of retinitis pigmentosa is about 1in 4000 for a total of more than 1 million aff ected individuals.The mechanism of the gradual death of conesis one of the key unsolved mysteries of RP. Increasing evidence supports that oxidative stress is one of important causes that may be common across RP isorders.Mitochondrial DNA (mtDNA) is constantly subjected to damage by many cellular to a greater extent than nuclear DNA. The efficiency of repair of damaged DNA depends on the activities of many DNA repair enzymes.To determine whether enhanced repair resulting from augmented expression of hOGG1 could also protect 661w cells against the deleterious effects of t-BHP and photoreceptors of rds mice , we used MTS-OGG1-pcDNA3.1+ transfected cells to conditionally express hOGG1 in mitochondria.Therefore, targeting DNA repair enzymes into cell mitochondria could be a potential therapeutic strategy for preventing or delaying the onset of this Retinal degeneration diseases.