The role of Crim-1 in lens development and eye disease.

我们最近分离了一个新的基因（Crim1），并表明它在眼睛发育过程中强烈表达。其蛋白结构提示其可能调控TGF超家族和胰岛素- igfs两个生长因子家族的活性。这些生长因子影响许多影响正常和病理发育事件的细胞类型的行为。例如，在晶状体中，TGF 1可诱导上皮细胞和早期分化纤维发生白内障改变；然而，TGF信号似乎是纤维细胞成熟后期事件所必需的。白内障是致盲的主要原因，当晶状体细胞结构被破坏或蛋白质聚集异常时就会出现白内障。在人类中，在眼部外伤、眼部手术或与其他疾病相关的情况下，可发生白内障。这些白内障的特点是囊下纤维化斑块的发展，使视力模糊。我们已经证明，TGF存在下培养的晶状体可以模拟这些斑块的产生，这表明这些白内障是由TGF的不适当激活引起的。TGF在晶状体中表达，在晶状体周围的眼介质中含量丰富。因此，似乎需要对TGF的生物利用度进行复杂的调控；上皮细胞和年轻的纤维细胞需要保护免受其白内障的影响，而较老的纤维需要TGF信号来成熟和或存活。Crim1在晶状体中的表达模式与其在晶状体中抑制TGF的关键作用相一致。因此，我们假设Crim1可能通过调节TGF超家族成员和胰岛素- igf在晶状体中发挥重要作用。我们预测，Crim1维持晶状体上皮表型，促进早期纤维分化。如果是这样的话，这可能会对设计预防或减缓疾病的分子策略产生影响，比如各种形式的人类白内障。

We have recently isolated a novel gene (Crim1) and shown it to be strongly expressed during eye development. Its protein structure indicates that it may act to regulate the activities of two growth factor families, the TGF superfamily and the insulin-IGFs. These growth factors effect the behaviour of many cell types that influence events in normal and pathological development. For example in the eye lens, TGF 1 can induce cataractous changes in epithelial cells and early differentiating fibres; however, TGF signalling appears to be required for events in late stages of fibre cell maturation. Cataract is the leading cause of blindness and arises when lens cell architecture is disrupted and-or proteins aggregate abnormally. In humans, following ocular trauma, eye surgery, or in association with other diseases, cataracts can develop. These cataracts feature the development of subcapsular fibrotic plaques which obscure vision. We have shown that lenses cultured in the presence of TGF can mimic production of these plaques suggesting that these cataracts result from inappropriate activation of TGF . TGF is expressed in the lens and is abundant in the ocular media that bathes the lens. Thus, it appears that complex regulation of TGF bioavailability is required; epithelial cells and young fibre cells need to be protected from its cataractogenic effects, whereas older fibres require TGF signalling for maturation and-or survival. The expression pattern of Crim1 in the lens is consistent with it having a key role in inhibiting TGF in the lens. Thus, we hypothesise that Crim1 plays important roles in the lens, possibly via the modulation of members of the TGF superfamily and insulin-IGFs. We predict that Crim1 acts to maintain the lens epithelial phenotype and facilitate events in early fibre differentiation. If so, this may have implications for devising molecular strategies for preventing or slowing diseases, such as the various forms of human cataract.