NO-cGMP信号通路对豚鼠形觉剥夺性近视的调控

Regulation role of nitric oxide-cyclic GMP signaling pathway in form-deprivation myopia of guinea pig

目的建立豚鼠形觉剥夺性近视动物模型,观察一氧化氮-环磷酸鸟苷(NO-cGMP)信号通路在视网膜上的动态表达,探讨其在近视发病机制中的作用。方法豚鼠分为3组:未遮盖组(Ⅰ)、遮盖2周组(Ⅱ)、遮盖3周组(Ⅲ),其中右眼遮盖为实验眼,左眼为自身对照眼。行视网膜检影和眼轴测量,原位杂交法检测神经细胞性一氧化氮合酶(ncNOS)的表达,放射免疫法检测c-GMP的含量,并对ncNOS和c-GMP的表达行直线相关分析。结果Ⅱ组、Ⅲ组实验眼随形觉剥夺时间延长近视形成,眼轴延长。ncNOS主要表达在豚鼠视网膜的内核层(INL)及神经节细胞层(GCL),ncNOS及cGMP随形觉剥夺时间的延长明显上调,两者具有高度相关性。结论NO-cGMP信号通路在豚鼠视网膜上有表达,形觉剥夺可明显上调视网膜上NO-cGMP信号通路的表达,该信号通路可能参与了近视的调控。

Objective Form-deprivation myopia was induced in guinea pig to characterize the changes of nitric oxidecyclic GMP signaling pathway in form-deprivation myopia （FDM） of guinea pig＇s retina and explore the possible mechanism of myopia. Methods Sixty three-week-old guinea pigs were assigned to three groups：group Ⅰ was normal guinea pigs（20） ;in group Ⅱ ,the right eyes （20 guinea pigs） underwent monocular form-deprivation by faeemask for 2 weeks. For group Ⅲ ,the right eyes from other 20 guinea pigs were monoeularly form-deprivated by faeemask for 3 weeks. The left eyes of all animals were used as self-controls. The refraction and axial length of animal eyes were detected and measured using A-type sonography. The expression of neNOS was detected by in situ hybridization,and cyclic GMP level in retina was detected using radioimmunoehemistry. The relationship between neNOS and cyclic GMP expression in retina was correlated using Bivariate correlations analysis. Results In group Ⅱ,the right eyes of guinea pigs showed a mild myopia status（ - 1.58 D） ,and the left eyes presented a mild hypermetropia status （ ＋ 2.50 D）. The axial length in the right eyes was elongated slightly in comparison with the left eyes （ P 〈 0.05 ）. In group Ⅲ ,the right eyes displayed a medium myopia （ - 3.42 D）, and the left eyes were in mild hypermetropia （ ＋ 1.82 D）. The axial length in the right eyes were extended dramatically in comparison with the left eyes （P 〈 0. 05）. In situ hybridization analysis showed that majority of neNOS located in retinal inner nuclear layer and ganglion cell layer. The expression of ncNOS and e-GMP was upregulated obviously in the right eyes compared with left eyes, showing a significant difference between them （ P 〈 0.05 ）. The expression of ncNOS was positively correlated with c-GMP in retina with the correlation coefficient 0. 941 （ P 〈 0. 001 ）. Conclusion The nitric oxide-cyclic GMP signaling pathway is expressed in retina of the guinea pig. Form-deprivation can activate nitric oxide-cyclic GMP signaling pathway,which may play an important role in the development of myopia.