Regulation of lens cell behaviour by RTK antagonists, Sef and Sprouty.

白内障，即眼睛透镜失去透明度，是世界性失明的主要原因。白内障的治疗取决于对正常和白内障透镜中分子过程的更好理解。透镜的生长受上皮细胞的受控增殖及其局部分化成纤维的调节。由于这种紧密调节的破坏导致白内障，识别控制细胞增殖和分化的分子将提供对白内障形成所涉及的机制的见解。例如，在白内障手术之后，许多患者发展出由残留的透镜细胞引起的后发性白内障。这些残留的细胞与正常透镜中受到严格调控的细胞不同，它们分裂和分化形成继发性白内障。本研究的主要目的是了解哪些分子调节透镜细胞的增殖和分化。生长因子是细胞行为的关键调节因子，我们的研究提供了证据表明FGF生长因子通过影响细胞增殖和分化在透镜中发挥关键作用。我们最近发现了透镜中FGF的抑制剂，称为Sprouty和Sef;在其他系统中显示的分子可有效阻断FGF细胞内信号传导途径。为了了解如何Sef和Sprouty调节透镜细胞增殖和纤维分化，我们计划检查是什么调节他们的表达，更重要的是他们的作用，FGF诱导的细胞信号在正常的透镜生物学。为此，我们将使用一个完善的外植体培养系统，以监测这些内源性抑制剂对生长因子诱导的透镜细胞增殖和分化的有效性，以及使用转基因小鼠技术，以确定他们在原位发挥的作用。通过了解正常透镜发育所必需的分子和细胞过程，我们可以更好地了解这些过程的中断如何导致白内障的形成。

Cataract, the loss of transparency of the eye lens, is a major cause of world blindness. A cure for cataract depends on a better understanding of the molecular processes in the normal and cataractous lens. Lens growth is regulated by controlled proliferation of epithelial cells and their localised differentiation into fibres. As disruption to this tight regulation leads to cataract, identifying the molecules that control cell proliferation and differentiation will provide insights into the mechanisms involved in cataract formation. Following cataract surgery, for example, many patients develop aftercataract which results from residual lens cells. These residual cells, unlike those tightly regulated in the normal lens, divide and differentiate to form a secondary cataract. The main aim of this study is to understand what molecules regulate the proliferation and differentiation of lens cells. Growth factors are key regulators of cell behaviour and our studies provide evidence that FGF growth factors play pivotal roles in the lens by influencing cell proliferation and differentiation. We have recently identified inhibitors of FGF in the lens, called Sprouty and Sef; molecules shown in other systems to effectively block FGF intracellular signalling pathways. To understand how Sef and Sprouty regulate lens cell proliferation and fibre differentiation, we plan to examine what regulates their expression, and more importantly their role in FGF-induced cell signalling in normal lens biology. To do this, we will use a well established explant culture system to monitor the effectiveness of these endogenous inhibitors on growth factor-induced lens cell proliferation and differentiation, as well as use transgenic mice technology to determine the role they play in situ. By understanding the molecular and cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.