Form-deprivation Myopia Group Research Articles

Scleral TGF-β1 and Smad3 expression is altered by TCM Bu Jing Yi Shi Tablets in guinea pigs with form-deprivation myopia

ObjectiveTo explore whether the traditional Chinese medicine (TCM) Bu Jing Yi Shi Tablets alters the expression of scleral TGF-β1 and Smad3 in guinea pigs with form-deprivation myopia (FDM). MethodsSixty-five guinea pigs were randomly divided into control, model, low-, medium-, and high-dose treatment groups. Except for the control group, FDM was induced by covering the right eye of each animal with opaque latex. The treatment groups were gavaged with different suspension concentrations of Bu Jing Yi Shi Tablets. Refraction and axial length were performed before and after myopia induction. At the end of the experiment, all right eyes were extracted, and scleral sections were prepared for staining and TGF-β1 and Smad3 immunohistochemistry. Scleral thickness and area, the scleral fibroblast quantity, and scleral TGF-β1 and Smad3 expressions were measured. ResultsThe 5 FDM groups had the same initial axial length and diopter, the final diopter and axial length of the model group were significantly increased compared with the control group and treatment groups (P < .01). The axial length of each treatment group decreased as the dose decreased compared with the model group (P < .01); the total scleral area (P < .05–.01) and the number of scleral fibroblasts (P < .01) in the model group were significantly lower than the treatment groups. Both the TGF-β1 and Smad3 integral optical densities in the model group were significantly lower than the control and medium- and high-dose treatment groups (P < .01). TGF-β1 and Smad3 mRNAs in the model group were decreased compared with the control group, but increased in expression after treatment. ConclusionBu Jing Yi Shi Tablets may restore the expression of scleral TGF-β1 and Smad3 in FDM guinea pigs and impede myopia development.

The sonic hedgehog signaling pathway induces myopic development by activating matrix metalloproteinase (MMP)-2 in Guinea pigs.

PurposeTo investigate whether the Sonic hedgehog (Shh) signaling induces myopic development by increasing the expression of matrix metalloproteinase (MMP)-2 in guinea pigs.MethodsA translucent diffuser was glued onto the right eye to induce form-deprivation myopia (FDM) in 10 guinea pigs. Four guinea pigs were served as a control group. The other 100 guinea pigs were subdivided into 5 groups (20 per group) and received a 10 µl intravitreal injection every 2 days for 4 times. Two groups were injected with 20 or 50 µg/ml Shh amino-terminal peptide (Shh-N) into the right eye and 0.1% bovine serum albumin into the other. FDM was induced in the right eyes of the three cyclopamine-treated groups and both eyes were injected with 50, 100, or 200 µg/ml cyclopamine. Retinoscopic refraction and eye dimensions were assessed on Day 14 of treatment. MMP-2 protein expression was determined in both scleras by western blotting.ResultsBoth concentrations of Shh-N stimulated myopic development and axial growth as compared with control eyes. Myopia and axial elongation were significantly greater in the 50 µg/ml than in the 20 µg/ml Shh-N group (P<0.001 and P = 0.0019, respectively). All three doses of cyclopamine significantly attenuated myopic development compared with the FDM group (P<0.0001). Cyclopamine at 100 or 200 µg/ml significantly reduced axial elongation compared with the FDM group (P = 0.044 and P = 0.001, respectively). FDM-induced myopia and axial elongation were significantly greater in the 50 µg/ml than in the 200 µg/ml cyclopamine group (P<0.0001 and P = 0.008, respectively). MMP-2 expression was significantly greater in Shh-N–treated eyes than in the control eyes, and was lower in the cyclopamine plus FDM groups than in the FDM group.ConclusionsThe Shh signaling pathway induces myopic development by activating MMP-2 in guinea pigs.

The correlation between the regulation of recombinant human IGF-2 on eye growth and form-deprivation in guinea pig

By investigating the effects of recombinant human IGF-2 (rhIGF-2) on the diopter, axial eye length and the expression of IGF-2 in non-form-deprivation (FD) and FD eyes of guinea pig, we tried to elucidate the relationship between the effects of rhIGF-2 on eye growth and FD in guinea pig. Eighty 3-week-old guinea pigs were included in the study, which were divided into two groups randomly. Group A (n = 40) was the non-FD group, Thirty-two guinea pigs received intravitreal injections of either 1 ng, 10 ng, 100 ng rhIGF-2 or bovine serum albumin (BSA) to the right eye; eight guinea pigs who received no intravitreal injections served as control. Group B (n = 40) was the FD group; the right eyes were form-deprived, and received the same disposals as group A. The diopter and the axial eye length of all guinea pigs were measured at day 14. The expression of IGF-2 in the retina was measured by Western blot. After 14 days, FD eyes were high myopia. The axial length of FD eyes was significant for longer than that of non-FD eyes. The expression of IGF-2 in the retina of FD eyes was up-regulated. In non-FD group, there was no significant difference in the diopter and axial eye length among rhIGF-2 injection eyes, BSA injection eyes and control eyes, but the expression of IGF-2 in the retina of 10 ng and 100 ng rhIGF-2 injection eyes was obviously down-regulated. In the FDM (form-deprivation myopia) group, the myopic diopter and axial eye length increased in 10 ng and 100 ng rhIGF-2 injection eyes compared with those in BSA injection eyes and control eyes. The level of IGF-2 expression in the retina of 10 ng and 100 ng rhIGF-2 injection eyes was obviously down-regulated. The diopter and expression of IGF-2 in the retina of rhIGF-2 injection eyes was negatively correlated with the dose of each injection, which was positively correlated with the axial length. RhIGF-2 intravitreous injection does not affect the diopter and axial length in non-FD eyes of guinea pig, while it can induce a significant increase in myopic diopter and axial length of FD eyes. RhIGF-2 can promote the development of FDM on the condition of FD.