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R. Schippert, C. Brand, F. Schaeffel, M.P. Feldkaemper; Transcriptional Control of MMP–2, TIMP–2 and TGFß–2 mRNA in the Chick Sclera by Imposed Defocus, and the Effects of Intravitreal Atropine . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3341.
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Purpose: To learn more about the visually–induced transcriptional regulation in the sclera, the expression kinetics of gelatinase–A (MMP–2), tissue inhibitor of matrix metalloproteinase–2 (TIMP–2) and transforming growth factor beta–2 (TGFß–2) mRNA were studied, following imposed myopic and hyperopic defocus. Since atropine can inhibit myopia development, the effect of intravitreal atropine injection on these genes was also examined. Methods: Myopia and hyperopia were unilaterally induced in 8 to 11 days old male white leghorn chickens using negative (–7D) and positive (+7D) lenses for different durations (4h, 24h, 72h). All contralateral eyes wore a plano lens, and bilaterally plano lens–treated animals served as additional controls. Relative mRNA levels of MMP–2, TIMP–2 and TGFß–2 in the two scleral layers were determined by semi–quantitative Real–Time PCR. Atropine (12.5 µl containing 750 µg) or saline were bilaterally injected in the vitreous body 24 hours before preparation. Results: The MMP–2/TIMP–2 ratio increased in both scleral layers in the contralateral eyes of the negative lens treated animals. In the same group, MMP–2 and TIMP–2 mRNA levels increased after 24 hours in the fibrous layer. In the cartilaginous layer, a general up–regulation of MMP–2 expression over time was found, independently of the sign of imposed defocus. Treatment with positive lenses led to increased TIMP–2 mRNA levels after 4 hours of treatment. After 24 hours, TGFß–2 mRNA levels were regulated in the cartilaginous sclera in correlation with the sign of imposed defocus (higher in the positive lens treated eyes, and decreased in the negative lens treated eyes) and there was no co–regulation in the plano lens treated fellow eyes. Atropine had no effects on MMP–2, TIMP–2 or TGFß–2 mRNA levels in the sclera, compared to saline–injected eyes. Conclusions: TGFß–2 mRNA levels in the cartilaginous layer were regulated in correlation with the sign of imposed defocus. The changes were confined to the eyes which actually displayed altered growth. MMP–2 and TIMP–2 were not regulated by the sign of imposed defocus and were strongly co–regulated in the plano lens treated fellow eyes, or the mRNA levels did not change at all. These findings suggest that TGFß–2 is important in the control of eye growth by defocus, whereas MMP–2 and TIMP–2 mRNA are unspecifically responding during scleral remodelling. Atropine does not seem to act on scleral growth via transcriptional control of TGFß–2, but rather through other parallel signaling cascades.
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