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J. Su, Z. Zhang, C. Wildsoet; Myopic & Hyperopic Defocus Effects on Chick Scleral MMP-2, MMP-13, TGFß-2, and TIMP-2 mRNA Levels. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1740. doi: https://doi.org/.
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Based on previous findings of visually-induced transcriptional regulation of various proteins in the chick sclera1, we sought to investigate further the effects of myopic and hyperopic defocus on the mRNA expression levels of gelatinase-A (MMP-2), collagenase 3 (MMP-13), transforming growth factor beta-2 (TGFß-2), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), which are implicated in scleral remodeling and have the potential to be used to tailor novel biomaterials to treat high myopia.
Myopic or hyperopic defocus was imposed on White-Leghorn chicks (3 wks old) using -10 or +10D lenses for 4 & 48h. Fellow eyes were left untreated as controls. Scleral layers were harvested and separated in the afternoon, and relative mRNA levels of MMP-2, MMP-13, TIMP-2 and TGFß-2 were measured by real-time quantitative PCR. Statistical significance was computed by paired student’s t-test.
Significant changes in mRNA expression were observed for all 4 proteins, albeit not at all time points. Typically, the results for fibrous and cartilaginous layers showed opposite trends as did results for (+) and (-) lenses (Table 1). Expression levels in the fellow eyes of the 2 lens groups were not significantly different, i.e. there was no interocular yoking.Table 1. Increased (>), decreased (<), or similar (-) scleral mRNA expression in lens-treated vs fellow eyes at 4 or 48h. (*p < 0.001).
As reported by Schippert et al1, TGFß-2 expression showed an early increase with (+) lenses in both scleral layers, similar to our finding in retinal pigment epithelium after 48h lens wear, and consistent with a role as an inhibitory growth modulator. However, the transient nature of its upregulation suggests additional growth modulatory influences on the latter. The cartilage expression patterns for MMP-2 & -13 are consistent with the opposite directions of growth induced by (+) and (-) lenses, only TIMP-2 showed robust expression changes in fibrous sclera. Their suitability as targets for biomaterials to treat high myopia requires verification of such changes after long-term treatment.1Schippert, R., et al., 2006. Exp Eye Res, 82:710-719.
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