OPA3: a novel gene and mechanism in cataractogenesis

OPA3：白内障发生的新基因和机制

• 批准号: G0500790/1
• 负责人: Marcela Votruba
• 金额: $ 25.48万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0500790%2F1
• 关键词: OPA3; novel; gene; mechanism; cataractogenesis

Cataract is due to cloudiness in the lens of the eye and so far, to date, there is no known way to prevent this fronm happening with age. Cataract is the most common cause of visual loss in humans, with at least 25 million blind and 110 million visually impaired world-wide. Despite surgery the number of patients who are blind world-wide increases steadily year on year. Adult cataract has been shown to have an environmental and a genetic component and there are over 20 cataract loci 10 genes for inherited cataracts. Recently, two heterozygous missense mutations in a new gene called OPA3 have been reported in patients with cataract (particularly the blue-dot type) and optic atrophy. The function of the OPA3 protein is not known, but it appears that it is targeted to mitochondria, which are tiny sub-cellular organelles. From what we know of the mechanism of development of the lens of the eye it appears highly likely that the OPA3 gene will prove interesting in the study of cataract formation. The mechanisms of programmed cell death (apoptosis) and the processes by which immature lens fibre cells lose their organelles and nuclei and become transparent are thought to be related. There is some evidence that OPA3 may act in an anti-apoptotic role and therefore it is postulated to be the first gene to cause cataractogenesis by this mechanism. We plan to screen blue-dot cataract families and individuals for mutation in OPA3. We also plan to explore the expression of OPA3 in the eye and lens in developing and adult tissue. Lastly, we shall explore the function of OPA3 using cell lines and a mouse model.

白内障是由于眼睛的透镜混浊，迄今为止，还没有已知的方法来防止这种随着年龄的增长而发生的晶状体混浊。白内障是人类视力丧失的最常见原因，全世界至少有2500万盲人和1.1亿视力受损者。尽管进行了手术，但全球失明患者的数量仍在逐年稳步增加。成人白内障已被证明具有环境和遗传成分，并且有超过20个白内障位点，其中10个基因是遗传性白内障。最近，在白内障（特别是蓝点型）和视神经萎缩的患者中报告了一种名为OPA3的新基因中的两个杂合错义突变。OPA3蛋白的功能尚不清楚，但似乎它靶向线粒体，线粒体是微小的亚细胞器。根据我们对眼睛透镜发育机制的了解，OPA 3基因极有可能在白内障形成的研究中被证明是有趣的。程序性细胞死亡（凋亡）的机制和未成熟的透镜纤维细胞失去细胞器和细胞核并变得透明的过程被认为是相关的。有一些证据表明OPA3可能起抗凋亡作用，因此推测它是通过该机制引起白内障发生的第一个基因。我们计划筛选蓝点白内障家庭和个人的OPA3突变。我们还计划探索OPA 3在发育和成人组织中的眼睛和透镜中的表达。最后，我们将使用细胞系和小鼠模型探索OPA3的功能。