Isoform-specific changes in scleral transforming growth factor-β expression and the regulation of collagen synthesis during myopia progression
Isoform-specific changes in scleral transforming growth factor-β expression and the regulation of collagen synthesis during myopia progression
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DOI：
10.1074/jbc.m400381200
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发表时间：
2004-04-30
影响因子：
4.8
通讯作者：
McBrien, NA
中科院分区：
文献类型：
--
作者：
Jobling, AI;Nguyen, M;McBrien, NA
高度近视的发生与巩膜细胞外基质生化改变有关。以往的研究强调了胶原周转在这一过程中的重要性，但目前还不清楚哪些因素控制巩膜重塑。本研究使用近视的哺乳动物模型来研究TGF（转化生长因子）-β 1、-β 2和-β 3影响近视中巩膜重塑的能力。RT-PCR证实了所有哺乳动物TGF-β亚型在巩膜组织和巩膜成纤维细胞中的存在。通过单眼剥夺图案视觉实验性诱导近视，并根据治疗持续时间（1或5天）将动物分配至两组。每种亚型的下调在近视发展仅1天后就很明显（TGF-β 1，-32%; TGF-β 2，-27%; TGF-β 3，-42%）。尽管TGF-β 1和TGF-β 3表达的降低在两个时间点之间相对恒定，但在第1天（-27%）和第5天（-50%）之间发现TGF-β 2的差异下调。使用原代巩膜成纤维细胞的体外实验证明了所有同种型以剂量依赖性方式增加胶原蛋白产生的能力。TGF-β水平的变化与近视诱导过程中的变化相似，导致胶原蛋白合成减少了15%，这与先前在体内报告的结果在性质上相似。这些数据代表了TGF-β 3在巩膜中表达的第一个证明，并暗示所有三种TGF-β亚型在近视发展期间控制巩膜重塑。此外，TGF-β表达水平的早期改变可能反映了这些细胞因子在调节控制近视眼生长的视网膜巩膜信号中的作用。
The development of high myopia is associated with altered scleral extracellular matrix biochemistry. Previous studies highlight the importance of collagen turnover in this process, yet it is unclear which factors control scleral remodeling. This study used a mammalian model of myopia to investigate the capacity of TGF (transforming growth factor)-beta1, -beta2, and -beta3 to influence scleral remodeling in myopia. RT-PCR confirmed the presence of all mammalian TGF-beta isoforms in scleral tissue and scleral fibroblasts. Myopia was experimentally induced via monocular deprivation of pattern vision, and animals were allocated to two groups depending on the duration of treatment ( 1 or 5 days). Downregulation of each isoform was apparent after only 1 day of myopia development (TGF-beta1, -32%; TGF-beta2, - 27%; TGF-beta3, - 42%). Whereas the decrease in TGF-beta1 and -beta3 expression was relatively constant between the two time points, differential down-regulation of TGF-beta2 was found between days 1 (-27%) and 5 (-50%). In vitro experiments, using primary scleral fibroblasts, demonstrated the capacity of all isoforms to increase collagen production in a dose-dependent manner. Changes in TGF-beta levels, which mimicked those during myopia induction, caused an similar to15% reduction in collagen synthesis, which is qualitatively similar to those previously reported in vivo. These data represent the first demonstration of TGF-beta3 expression in the sclera and implicate all three TGF-beta isoforms in the control of scleral remodeling during myopia development. In addition, the early alterations in TGF-beta expression levels may reflect a role for these cytokines in mediating the retinoscleral signal that controls myopic eye growth.