Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery
Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery
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DOI：
10.1167/iovs.05-0194
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Norton, TT
中科院分区：
文献类型：
--
作者：
Siegwart, JT;Norton, TT
目的.在幼年树鼩中，将负屈光力的透镜置于眼睛前方，可增加眼轴伸长，并使屈光状态发生近视性变化，以补偿透镜的屈光力。在透镜补偿期间发生巩膜组织重塑和巩膜的机械性质的调节。在这项研究中，研究了在负透镜代偿过程中和恢复过程中，三种MMP和三种TIMP的巩膜mRNA水平变化的时间过程，以确定是否与巩膜的机械性能和轴向伸长率的变化存在时间相关性。采用竞争性RT-PCR方法检测接受单眼-5-D镜片治疗1、2、4或11天，或接受11天-5-D镜片治疗后恢复2或4天的树鼩巩膜中MT 1-MMP、MMP-2、MMP-3、TIMP-1、TIMP- 2和TIMP- 3的mRNA水平。与对照眼相比，负透镜治疗1 - 4天后，治疗眼MT 1-MMP和MMP-2 mRNA水平显著升高，TIMP- 3水平降低。当治疗眼补偿了透镜时，治疗11天时不存在这些差异效应。恢复2天后，所有三种TIMP的水平在双眼中均升高。MT 1-MMP、MMP-2和TIMP- 3 mRNA水平的差异变化均局限于治疗眼，并与眼轴伸长、屈光状态和先前测量的蠕变率变化的差异变化存在时间相关性。所观察到的MT 1-MMP、MMP-2、TIMP- 2和TIMP- 3 mRNA的变化与视觉调节的MMP-2的MT 1-MMP活化和巩膜细胞外基质组分的MT 1-MMP降解一致。这些数据构成了视觉信号调节所选MMP和TIMP的基因表达以控制巩膜重塑、巩膜的机械性质、轴向伸长和屈光状态的进一步证据。
PURPOSE. In juvenile tree shrews, a minus-power lens placed in front of the eye produces increased axial elongation and a myopic shift in refractive state that compensates for the power of the lens. Scleral tissue remodeling and modulation of the mechanical properties of the sclera occur during lens compensation. In this study, the time course of changes in scleral mRNA levels of three MMPs and three TIMPs during compensation for a minus lens and during recovery was investigated, to determine which, if any, are temporally associated with changes in the mechanical properties of the sclera and the axial elongation rate.METHODS. Competitive RT-PCR was used to measure the levels of mRNA for MT1-MMP, MMP-2, MMP-3, TIMP-1, TIMP- 2, and TIMP- 3 in the scleras of tree shrews that had received either 1, 2, 4, or 11 days of monocular -5-D lens treatment, or 11 days of -5-D lens treatment followed by 2 or 4 days of recovery.RESULTS. Relative to their control eyes, treated eye MT1-MMP and MMP-2 mRNA levels were significantly higher, and TIMP- 3 levels were lower by 1 to 4 days of minus lens treatment. These differential effects were absent by 11 days of treatment when the treated eyes had compensated for the lens. The levels of all three TIMPs spiked upward in both eyes after 2 days of recovery. The differential changes in MT1-MMP, MMP-2, and TIMP- 3 mRNA levels were all restricted to the treated eye and were temporally associated with the differential changes in axial elongation, refractive state, and the previously measured changes in creep rate.CONCLUSIONS. The observed changes in MT1-MMP, MMP-2, TIMP- 2, and TIMP- 3 mRNA are consistent with visually modulated MT1-MMP activation of MMP-2 and with MT1-MMP degradation of scleral extracellular matrix components. These data constitute further evidence that visual signals modulate gene expression of selected MMPs and TIMPs to control scleral remodeling, the mechanical properties of the sclera, axial elongation, and refractive state.