Growth-factor induced signalling pathways involved in the regulation of lens cell behaviour

白内障，即眼球晶状体失去透明度，是世界上致盲的主要原因。白内障的治疗取决于对正常晶状体和白内障晶状体的分子过程有更好的了解。晶状体的生长受上皮细胞增殖的控制及其向纤维的精确局部分化的调节。由于这种严格调控的破坏导致白内障，确定控制细胞增殖和分化的分子可能为了解白内障形成的机制提供见解。例如，在白内障手术后，许多患者由于术后遗留的晶状体细胞的反应而出现后发性白内障。与正常晶状体中受到严格调控的细胞不同，这些残留细胞开始分裂和分化，试图形成新的晶状体。本研究的主要目的是了解晶状体细胞增殖和分化的调控因素。生长因子是细胞行为的关键调节因子，我们的研究提供了FGF、PDGF和IGF生长因子家族成员通过影响细胞增殖和分化在晶状体中发挥关键作用的证据。生长因子通过激活特定的细胞表面受体来刺激细胞过程。一旦被激活，这些受体打开特定的细胞内信号通路，导致特定的细胞反应。为了了解不同的生长因子如何介导和调节晶状体细胞增殖和纤维分化，我们计划研究FGF-、PDGF-和igf诱导的信号在正常晶状体生物学中的作用。为了做到这一点，我们将使用一个完善的晶状体外植体培养系统来剖析特定受体激活的下游信号通路，并将其与特定的细胞反应联系起来。通过了解正常晶状体发育所必需的细胞过程，我们可以更好地了解这些过程的破坏是如何导致白内障形成的。

Cataract, the loss of transparency of the eye lens, is a major cause of blindness in the world. 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 precise localised differentiation into fibres. As disruption of this tight regulation leads to cataract, identifying the molecules that control cell proliferation and differentiation may provide insights into the mechanisms involved in cataract formation. Following cataract surgery, for example, a number of patients develop aftercataract which results from the response of lens cells remaining after surgery. These residual cells, unlike those tightly regulated in the normal lens, begin to divide and differentiate in an attempt to form a new lens. The main aim of this study is to understand what regulates the proliferation and differentiation of lens cells. Growth factors are key regulators of cell behaviour and our studies provide evidence that members of the FGF, PDGF and IGF growth factor families play pivotal roles in the lens by influencing cell proliferation and differentiation. Growth factors stimulate cellular processes by activating specific cell surface receptors. Once activated, these receptors switch on specific intracellular signalling pathways leading to a specific cellular response. To understand how different growth factors mediate and regulate lens cell proliferation and fibre differentiation, we plan to examine the role of FGF-, PDGF- and IGF-induced signalling in normal lens biology. To do this, we will use a well established lens explant culture system to dissect the signalling pathway(s) downstream of specific receptor activation and correlate this with a specific cellular response. By understanding the cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.