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.

我们最近分离了一个新型基因（Crim1），并在眼睛发育过程中表达了强烈表达。它的蛋白质结构表明它可以调节两个生长因子家族的活性，即TGF超家族和胰岛素-IGF。这些生长因素影响许多影响正常和病理发展事件的细胞类型的行为。例如，在眼镜中，TGF 1可以诱导上皮细胞和早期区分纤维的白内障变化。但是，在纤维细胞成熟的后期事件似乎需要TGF信号传导。白内障是失明的主要原因，当晶状体细胞结构被破坏并且蛋白质异常聚集时会产生。在人类中，遵循眼部创伤，眼科手术或与其他疾病相关，可以发展出白内障。这些白内障的特征是遮盖视力的下囊纤维斑块的发展。我们已经表明，在存在TGF的情况下培养的透镜可以模仿这些斑块，这表明这些白内障是由于TGF的不适当激活而引起的。 TGF在镜头中表达，在沐浴镜头的眼部介质中很丰富。因此，似乎需要对TGF生物利用度的复杂调节。需要保护上皮细胞和幼纤维细胞免受白内障作用的影响，而较老的纤维需要TGF信号传导才能成熟和或生存。镜头中Crim1的表达模式与其在抑制晶状体中TGF中具有关键作用一致。因此，我们假设Crim1可能通过TGF超家族和胰岛素-IGF的成员的调节在镜头中起重要作用。我们预测，Crim1的作用是维持晶状体上皮表型并促进早期纤维分化的事件。如果是这样，这可能对制定分子策略来预防或放缓疾病，例如各种形式的人白内障。