环磷酸鸟苷在遗传性视网膜变性中的研究进展  

Research progress of cyclic guanosine monophosphate in inherited retinal degeneration

作　　者：刘子实 李彤[1] 孙晓东[1] Liu Zishi;Li Tong;Sun Xiaodong(Department of Ophthalmology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,National Clinical Research Center for Ophthalmic Diseases,Shanghai Key Laboratory of Fundus Diseases,Shanghai Engineering Center for Visual Science and Photomedicine,Shanghai 200080,China)

机构地区：[1]上海交通大学附属第一人民医院眼科,国家眼部疾病临床医学研究中心,上海市眼底病重点实验室上海眼视觉与光医学工程技术研究中心,上海200080

出　　处：《中华眼底病杂志》2024年第11期898-904,共7页Chinese Journal of Ocular Fundus Diseases

基　　金：国家自然科学基金(82101168);上海市科学技术委员会项目(21ZR1451500)。

摘　　要：遗传性视网膜变性(IRD)是一组具有高度遗传异质性和临床异质性的眼底病,目前已发现超过300种基因突变与IRD有关。胞内第二信使环磷酸鸟苷(cGMP)的失调在多种IRD的发生和发展中发挥重要作用。cGMP在光感受器细胞中参与光转导过程,当cGMP水平异常增高,则会过度激活蛋白激酶G和环核苷酸门控通道,分别引起蛋白质磷酸化和Ca^(2+)超载,这两种依赖cGMP的途径可能单独或共同驱动光感受器细胞退行性病变和死亡;因此,减少cGMP合成或阻止cGMP下游信号传导可作为疾病的治疗策略。研究cGMP失调在光感受器细胞退化过程中的分子机制可以更加全面地阐述IRD发病原因,同时为寻找新治疗靶点和设计治疗方案提供思路。Inherited retinal degeneration(IRD)is a group of fundus diseases characterized by a high degree of genetic heterogeneity and clinical heterogeneity,and more than 300 genetic mutations have been identified in association with IRD.Dysregulation of the intracellular second messenger cyclic guanosine monophosphate(cGMP)plays an important role in the development of IRD.cGMP participates in phototransduction process in photoreceptors.Abnormally elevated cGMP over-activate protein kinase G and cyclic nucleotide-gated channel,causing protein phosphorylation and Ca*overload,respectively,and these two cGMP-dependent pathways may individually or collectively drive photoreceptor degenerative lesions and death;therefore,reducing cGMP synthesis and blocking downstream signaling can be considered as treatment strategies.Investigating the molecular mechanisms of cGMP dysregulation in photoreceptor degeneration may provide a more comprehensive picture of the pathogenesis of IRD,as well as ideas for finding new therapeutic targets and designing therapeutic programs.

关 键 词：遗传性视网膜变性 环磷酸鸟苷 光转导 综述 

分 类 号：R774.1[医药卫生—眼科]