The Role Of Collagen-binding Integrin Receptors In Scleral Remodelling During Induced Myopia

Objective To observe the expression of the collagen-binding integrin α1、α2 and β1 in sclera of the guinea pig form-deprivation myopia(FDM), and to investigate the role of those integrins in sclera remodeling process during FDM development and recovery.Methods 160 young guinea pigs, aged 2 to 3 weeks, were randomized into experimental group(n=80) and normal control group(n=80). FDM models were monocular deprived by placement of a facemask over the right eye in the experimental group, and the fellow eyes served as the contralateral control eyes. The guinea pigs in the normal control group were raised with both eyes untreated. The FDM eyes were monocular deprived for 1, 2 and 4 weeks, and recovery 1, 3, 5, 7, 14 days after occluded 4 weeks. Optical measurements and axial length were accomplished at all of the timepoints. The histological analysis was applied to assess the posterior sclera changes, and the electron microscope was used to study the ultra-structure of sclera. The immunohistochemical staining and quantitative real-time PCR(QRT-PCR) were applied to investigate the expression of integrin α1、α2 and β1 protein and m RNA.Results After 2 and 4 weeks, compared with the fellow eyes and the normal control group, the refraction diopter of the experimental group was(-3.00±0.50)D and(-5.50±1.08)D, and the axial length elongated(0.22±0.06)mm and(0.49±0.11)mm, showing significant differences respectively(P<0.05); but on 1 week, the statistics showed no difference among those groups(P>0.05). After re-exposure, the right eyes of guinea pigs in the experimental group experienced re-normalization and the refraction was rapidly recovered in the initial 7 days(P>0.05); and the axial length gradually shortened, and there were statistically non-significant after 14 days recovery(P>0.05). The morphological observation of sclera found that the nucleus of fibroblasts was distorted and the sclera became thinner in FDM eyes. The electron microscope showed that the posterior sclera collagen fiber arrangement of guinea pigs with FDM was disordered, with the fiber diameters smaller. The scleral integrin α1、α2 and β1 m RNA and protein expression in FDM eyes was significantly lower than that in the controls after monocular deprived 1 week(P<0.05). On the first day after occlusion had been removed, the expression of integrin α1 、 α2 and β1 was up-regulated but lower than that in the controls(P<0.05), and the difference wasnon-significant after 7 days recovery(P>0.05). The difference of all the above statistics between contralateral control eyes and the normal control group was not remarkably(P>0.05).Conclusions Guinea pigs aged 2 to 3 weeks with form-deprivation can experience re-normalization after recovery, along with the shortening of the axial length. The main recovery stage of ocular biometric parameters is in the initial 7 days. In the FDM induced period, the sclera became thinner and the ultra-structure was changed with the fiber diameters smaller, indicating that the development of experimental myopia is an abnormal remodeling process of sclera. The expression of integrin α1、α2 and β1 in FDM sclera was found to be lower, but can be restored during the recovery period. This suggests that collagen-binding integrin α1、α2 and β1 might be involved in the pathogenesis of myopia, and might play a protective role in the myopic mechanism. Further study needs to be done on the mechanism of the scleral remodeling in myopia.