The Role Of Smad1 During Refractive Development And Form-deprivation Myopia Development In The C57BL/6 Mice

PUR POSE To observe the expression of Smad1 as BMP/TGF-β signaling pathyway downstream factor during refractive development a nd form-deprivation myopia(FDM) development in C57BL/6 mice model, and to explore the role of Smad1 during FDM development and refractive development.METHODS 96 C57BL/6 mice, approximately 21-day-old, were randomly divided into experimental group(n=48) and normal control group(n=48) which totally include four groups: Form-deprivation 7d group(FDM1W, n=16), Form-deprivation 21 d group(FDM3W, n=16), Form-deprivation 28 d group(FDM4W, n=16), FDM7 d normal control group(FDM1WNC, n=16) FDM21 d normal control group(FDM3WNC, n=16) and FDM28 d normal control group(FDM4WNC, n=16). Mice in monocular deprivation(MD) groups were treated with diffuser wearing on right eyes, and their left eyes were naturally exposed as their self-control group. The normal control groups were free of all the treatment, but the same measurements were performed at the same time-point. Optical measurements was accomplished at the end of the time-points. The histological analysis was applied to assess the changes of posterior wall of eyeball. The immunohistochemical staining, immunofluorescence assay and quantitative real-time PCR(QRT-PCR) were applied to investigate the expression of Smad1 protein and m RNA.RESULTS 1) There was no significant difference between each group before form deprivation. The normal control groups and self-control groups showed physiological farsighted development, the MD eyes demonstrated relatively myopization; 2) In FDM21 d and FDM28 d, a significant myopia shift had been induced in the treated eyes compared with the fellow eyes. Before and after experiment, refraction in FDM21 d group were respectively(4.43±0.92)and(1.93±0.68)D(P<0.05), and in FDM28 d group were respectively(4.66±0.66)and(0.91±0.51)D(P<0.05); the axial length elongated(16±12)um and(21±13)um, showing significant differences respectively(P<0.05), and compare with FDM21 d groups, the axial length in FDM28 d groups were elongated, the difference was statistically significant(P<0.05); but on 7d, the statistics showed no difference among those groups(P>0.05).; 3) Histopathologic examination showed retina(especially inner nuclear layer and inner plexiform layer) in experimental group were thinner than control groups; 4) Smad1 were expressed in retina, and compared with self-control groups and normal contro l groups, the expression of Smad1 in the retina of the experimental group was significantly decreased(P<0.01).CONCLUSION 1)Form-deprivation myopia can be induced in C57BL/6 mice; the diopter and axial length increased as MD prolonged; 2)Form deprivation could cause the retina(especially inner nuclear layer and inner plexiform layer) to become thinner than self-control groups and normal control groups; 3)The expression of Smad1 shows no changes in normal refractive development in C57BL/6 mice, while in the retina and sclera of form-deprivation myopia was down-regulated, suggested that Smad1 likely to be involved in the development of myopia as a protective signal transduction factor. Further study needs to be done on the mechanism of Smad1 in refractive development and form-deprivation myopia development...