Schmidt S Y, Lolley R N
J Cell Biol. 1973 Apr;57(1):117-23. doi: 10.1083/jcb.57.1.117.
Cyclic nucleotides have been implicated in the differentiation and function of the vertebrate retina. In the normal retina of DBA mice, the specific activity of cyclic-nucleotide phosphodiesterase (PDE), with cyclic-AMP as the substrate (cAMP-PDE), increases eightfold between the 6th and 20th postnatal day. Kinetic analysis of retinae from newborn mice reveals a PDE with a single Michaelis constant (K(m)) value for cyclic-AMP (low K(m)-PDE). After the 6th postnatal day, a second PDE with a high K(m) for cyclic-AMP (high K(m)-PDE) can be demonstrated. The appearance and increasing activity of the high K(m)-PDE coincides with the differentiation and growth of photoreceptor outer segments. Additionally, the high K(m)-PDE is shown by microchemical techniques to be concentrated in the photoreceptor cell layer and the low K(m)-PDE within the inner layers of the normal retina. In C3H mice afflicted with an inherited degeneration of the photoreceptor layer, the postnatal increase in the specific activity of cAMP-PDE is substantially lower than in the normal retina. The postnatal increase in the specific activity of cAMP-PDE in two regions of the brain of C3H mice is the same as in the normal strain. A deficiency in high K(m)-PDE activity in the C3H retina is evident on the 7th postnatal day, when the activity of low K(m)-PDE, photoreceptor morphology, and rhodopsin content of these retina are essentially normal. In the adult C3H retina, the PDE activity with cyclic-GMP and cyclic-UMP as substrates is significantly below that of the normal retina. These data indicate that an alteration in cyclic-AMP metabolism occurs before photoreceptor cell degeneration in the retinae of C3H mice.
环核苷酸与脊椎动物视网膜的分化和功能有关。在DBA小鼠的正常视网膜中，以环磷酸腺苷（cAMP）为底物的环核苷酸磷酸二酯酶（PDE）的比活性在出生后第6天到第20天之间增加了八倍。对新生小鼠视网膜的动力学分析显示，有一种PDE对环磷酸腺苷具有单一的米氏常数（K(m)）值（低K(m)-PDE）。出生后第6天之后，可以证明存在另一种对环磷酸腺苷具有高K(m)值的PDE（高K(m)-PDE）。高K(m)-PDE的出现和活性增加与光感受器外段的分化和生长相吻合。此外，微量化学技术表明，高K(m)-PDE集中在光感受器细胞层，而低K(m)-PDE则存在于正常视网膜的内层。在患有光感受器层遗传性退化的C3H小鼠中，cAMP-PDE的比活性在出生后的增加幅度明显低于正常视网膜。C3H小鼠大脑两个区域中cAMP-PDE的比活性在出生后的增加与正常品系相同。在出生后第7天，C3H视网膜中高K(m)-PDE活性的缺乏就很明显，此时这些视网膜的低K(m)-PDE活性、光感受器形态和视紫红质含量基本正常。在成年C3H视网膜中，以环磷酸鸟苷（cGMP）和环磷酸尿苷（cUMP）为底物的PDE活性明显低于正常视网膜。这些数据表明，在C3H小鼠视网膜光感受器细胞退化之前，环磷酸腺苷代谢就发生了改变。
