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

Crim-1 在晶状体发育和眼部疾病中的作用。

• 批准号: nhmrc : 142977
• 负责人: Prof Frank Lovicu
• 金额: $ 13.1万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-crim-1-eye-disease/78482
• 关键词: role; Crim; lens; development; eye

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.

我们最近分离出一个新的基因（EST 1），并显示它在眼睛发育过程中强烈表达。其蛋白质结构表明，它可能起到调节两个生长因子家族，TGF超家族和胰岛素-IGFs的活动。这些生长因子影响许多细胞类型的行为，这些细胞类型影响正常和病理发育中的事件。例如，在眼睛透镜中，TGF β 1可诱导上皮细胞和早期分化纤维中的白内障变化;然而，TGF β 1信号传导似乎是纤维细胞成熟晚期事件所需的。白内障是失明的主要原因，当透镜细胞结构被破坏和-或蛋白质异常聚集时就会发生。在人类中，在眼外伤、眼科手术或与其他疾病相关的情况下，可发展白内障。这些白内障的特征是发展为囊下纤维化斑块，使视力模糊。我们已经表明，在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在透镜中表达，并且在浸润透镜的眼介质中丰富。因此，似乎需要对TGF生物利用度进行复杂的调节;上皮细胞和年轻的纤维细胞需要受到保护，免受其白内障发生作用的影响，而老年纤维需要TGF信号传导来成熟和/或存活。透镜中TGF β 1的表达模式与其在透镜中抑制TGF β中具有关键作用一致。因此，我们推测，TGF β 1在透镜中起着重要作用，可能是通过调节TGF超家族成员和胰岛素-IGFs。我们预测，TRY 1的行为，以维持透镜上皮细胞的表型和促进早期纤维分化的事件。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，例如各种形式的人类白内障。