LIGHT‐INDUCED REDUCTION IN CYCLIC GMP OF RETINAL PHOTORECEPTOR CELLS IN VIVO: ABNORMALITIES IN THE DEGENERATIVE DISEASES OF RCS RATS AND rd MICE 1
LIGHT‐INDUCED REDUCTION IN CYCLIC GMP OF RETINAL PHOTORECEPTOR CELLS IN VIVO: ABNORMALITIES IN THE DEGENERATIVE DISEASES OF RCS RATS AND rd MICE 1
复制标题
光诱导体内视网膜感光细胞环 GMP 减少：RCS 大鼠和 rd 小鼠退行性疾病中的异常现象 1
DOI：
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发表时间：
1977
影响因子：
4.7
通讯作者：
Richard N. Lolley
中科院分区：
文献类型：
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作者：
Debora B. Farber;Richard N. Lolley
摘要：比较了光对皇家外科医学院（RCS）大鼠和 rd 小鼠退变视网膜中环 GMP 含量的影响与出生后成熟过程中对照视网膜的影响。在体内，光感受器外节发育后，对照大鼠或小鼠视网膜的环 GMP 含量呈光依赖性。对照动物的成熟视网膜在黑暗中具有高水平的环 GMP，在光照下会降低 40-50%。在 rd 小鼠疾病中，观察到光诱导的环 GMP 含量减少，而杆外节形态完好。 rd 感光细胞具有磷酸二酯酶，当通过冷冻干燥稳定时，其 Km 与对照感光细胞相似，并且明显的 Vmax 低于正常值。研究表明，发育中的视细胞的环 GMP 代谢存在异常，导致环 GMP 在整个细胞内积累，但这并不能阻止光介导的外节细胞器中环 GMP 的还原。在 RCS 营养不良中，在光感受器外节存在期间也观察到光诱导的环 GMP 含量减少。暗适应或光适应 RCS 视网膜的环 GMP 含量低于相应对照。生化和形态学观察表明，在视细胞变性发生之前，rd 视细胞中的环化 GMP 水平增加，而 RCS 视网膜感光细胞中的环化 GMP 水平降低。在详细了解环 GMP 在视觉细胞中的作用之前，有人认为 rd 和 RCS 光感受器中环 GMP 的高水平或低水平分别是由小鼠和大鼠疾病的病因学或组织病理学差异造成的。
Abstract— The effect of light on the content of cyclic GMP in degenerative retinae of Royal College of Surgeons (RCS) rats and rd mice was compared with that in control retinae during postnatal maturation. In vivo, the cyclic GMP content of retinae of control rats or mice is light‐dependent after photoreceptor outer segments develop. Mature retinae of control animals have high levels of cyclic GMP in the dark which are reduced 40–50% upon illumination. In the rd mouse disorder, a light‐induced reduction in cyclic GMP content is observed while the rod outer segments are morphologically intact. The rd photoreceptor cells possess a phosphodiesterase which, when stabilized by freeze‐drying, has a Km similar to that of control photoreceptors, and an apparent Vmax that is below normal. It is suggested that developing rd visual cells have an abnormality in cyclic GMP metabolism which results in the accumulation of cyclic GMP within the entire cell but which does not prevent the light‐mediated reduction of cyclic GMP in their outer segment organelles. In the RCS dystrophy, a light‐induced reduction in cyclic GMP content is observed also during the period when photoreceptor outer segments are present. The cyclic GMP content of dark‐ or light‐adapted RCS retinae is below that of the respective controls. Biochemical and morphological observations show that cyclic GMP levels increase in rd visual cells and that they are reduced in photoreceptor cells of RCS retina before the onset of visual cell degeneration. Until detailed knowledge of the role of cyclic GMP in the visual cells is known, it is suggested that high or low levels of cyclic GMP in rd and RCS photoreceptors, respectively, result from differences in the etiology or histopathology of the mouse and rat diseases.