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

白内障，即眼睛透镜失去透明度，是世界上致盲的主要原因。白内障的治疗取决于对正常和白内障透镜中分子过程的更好理解。透镜生长受上皮细胞受控增殖及其精确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可以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，许多患者发展后发性白内障，这是由手术后剩余的透镜细胞的反应引起的。与正常透镜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，试图形成新的透镜。本研究的主要目的是了解是什么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、PDGF和IGF生长因子家族的成员通过影响细胞增殖和分化在透镜中发挥关键作用。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，这些受体就会开启特定的细胞内信号传导途径，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透镜细胞增殖和纤维分化，我们计划研究FGF，PDGF和IGF诱导的信号传导在正常透镜生物学中的作用。为此，我们将使用完善的透镜外植体培养系统来剖析特异性受体激活下游的信号传导途径，并将其与特异性细胞反应相关联。通过了解正常透镜发育所必需的细胞过程，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 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.